PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 31497348-6 2019 We found that knockdown of LKB1 significantly promoted in vitro proliferation, adhesion, invasion, and metformin-induced apoptosis, and simultaneously enhanced activation of ERK and mammalian-target of rapamycin (mTOR) signaling pathways in LKB1-compenent U87 and T98 glioblastoma cells. Metformin 103-112 serine/threonine kinase 11 Homo sapiens 27-31 33887464-9 2021 Metformin treatment prompted apoptosis upon miR-17-overexpression only in LKB1WT cell lines, as well as in LWT/miR17H PDXs. Metformin 0-9 serine/threonine kinase 11 Homo sapiens 74-78 32934724-4 2020 The direct mechanisms of metformin include inhibition of the LKB1-AMP-activated protein kinase-mTOR, PI3K-Akt and insulin-like growth factor 1-related signaling pathways, which reduces the proliferation and promotes the apoptosis of EC cells. Metformin 25-34 serine/threonine kinase 11 Homo sapiens 61-65 30552782-7 2019 Suppression of LKB1 or promotion of AMP by metformin also abrogated the hyperproliferative phenotype caused by SIRT4 loss, which further confirmed that the LKB1/AMPKalpha/mTOR axis is required in SIRT4-deficiency-promoted HCC tumorigenesis. Metformin 43-52 serine/threonine kinase 11 Homo sapiens 156-160 31114366-3 2019 Metformin inhibits mTOR activity by activating ATM (ataxia telangiectasia mutated) and LKB1 (liver kinase B1) and then adenosine monophosphate-activated kinase (AMPK), and thus prevents protein synthesis and cell growth. Metformin 0-9 serine/threonine kinase 11 Homo sapiens 87-91 31114366-3 2019 Metformin inhibits mTOR activity by activating ATM (ataxia telangiectasia mutated) and LKB1 (liver kinase B1) and then adenosine monophosphate-activated kinase (AMPK), and thus prevents protein synthesis and cell growth. Metformin 0-9 serine/threonine kinase 11 Homo sapiens 93-108 30149143-0 2018 Metformin Enhances Cisplatin-Induced Apoptosis and Prevents Resistance to Cisplatin in Co-mutated KRAS/LKB1 NSCLC. Metformin 0-9 serine/threonine kinase 11 Homo sapiens 103-107 30710424-0 2019 Metformin and tenovin-6 synergistically induces apoptosis through LKB1-independent SIRT1 down-regulation in non-small cell lung cancer cells. Metformin 0-9 serine/threonine kinase 11 Homo sapiens 66-70 30710424-7 2019 Metformin in combination with tenovin-6 was found to be more effective in inhibiting cell growth than either agent alone in NSCLC cell lines with different liver kinase B1 (LKB1) status. Metformin 0-9 serine/threonine kinase 11 Homo sapiens 156-171 30710424-7 2019 Metformin in combination with tenovin-6 was found to be more effective in inhibiting cell growth than either agent alone in NSCLC cell lines with different liver kinase B1 (LKB1) status. Metformin 0-9 serine/threonine kinase 11 Homo sapiens 173-177 30710424-9 2019 The marked reduction in SIRT1 expression by combination of metformin and tenovin-6 increased acetylation of p53 at lysine 382 and enhanced p53 stability in LKB1-deficient A549 cells. Metformin 59-68 serine/threonine kinase 11 Homo sapiens 156-160 30710424-12 2019 The study concluded that metformin with tenovin-6 may enhance antitumour effects through LKB1-independent SIRT1 down-regulation in NSCLC cells. Metformin 25-34 serine/threonine kinase 11 Homo sapiens 89-93 30483811-9 2019 The present study also explored the role of metformin in the LKB1 signaling pathway. Metformin 44-53 serine/threonine kinase 11 Homo sapiens 61-65 30149143-7 2018 In preclinical experiments, metformin produced pro-apoptotic effects and enhanced cisplatin anticancer activity specifically in KRAS/LKB1 co-mutated patient-derived xenografts. Metformin 28-37 serine/threonine kinase 11 Homo sapiens 133-137 30149143-10 2018 Metformin synergizes with cisplatin against KRAS/LKB1 co-mutated tumors, and may prevent or delay the onset of resistance to cisplatin by targeting CD133+ cancer stem cells. Metformin 0-9 serine/threonine kinase 11 Homo sapiens 49-53 30149143-11 2018 This study lays the foundations for combining metformin with standard platinum-based chemotherapy in the treatment of KRAS/LKB1 co-mutated NSCLC. Metformin 46-55 serine/threonine kinase 11 Homo sapiens 123-127 26847819-0 2016 Metformin inhibits growth of human non-small cell lung cancer cells via liver kinase B-1-independent activation of adenosine monophosphate-activated protein kinase. Metformin 0-9 serine/threonine kinase 11 Homo sapiens 72-88 28761738-1 2017 PURPOSE: Our previous works demonstrated the ability of metformin to revert resistance to gefitinib, a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in non-small-cell lung cancer (NSCLC) EGFR/LKB1 wild-type (WT) cell lines. Metformin 56-65 serine/threonine kinase 11 Homo sapiens 223-227 26847819-3 2016 However, whether the antitumor effect of metformin is via the LKB1/AMPK signaling pathway remains to be determined. Metformin 41-50 serine/threonine kinase 11 Homo sapiens 62-66 29966520-2 2018 Apart from its hypoglycemic properties, metformin also inhibits the cell cycle by restricting protein synthesis and cell proliferation via regulating the LKB1/AMPL pathway. Metformin 40-49 serine/threonine kinase 11 Homo sapiens 154-158 29601127-0 2018 LKB1 obliterates Snail stability and inhibits pancreatic cancer metastasis in response to metformin treatment. Metformin 90-99 serine/threonine kinase 11 Homo sapiens 0-4 29601127-6 2018 Notably, metformin could increase Snail protein ubiquitination via augmenting the location of LKB1 at cytoplasm as well as increasing LKB1 expression. Metformin 9-18 serine/threonine kinase 11 Homo sapiens 94-98 29601127-6 2018 Notably, metformin could increase Snail protein ubiquitination via augmenting the location of LKB1 at cytoplasm as well as increasing LKB1 expression. Metformin 9-18 serine/threonine kinase 11 Homo sapiens 134-138 29601127-8 2018 Targeting the LKB1/FBXL14/Snail axis may represent a promising therapeutic strategy and metformin might be beneficial for PC therapy through activating the LKB1-mediated Snail ubiquitination pathway. Metformin 88-97 serine/threonine kinase 11 Homo sapiens 156-160 28494141-7 2018 Inhibition of LKB1 activity, a common upstream AMPK kinase, markedly reversed metformin-induced AMPK activation, RUNX2 expression and nuclear localization. Metformin 78-87 serine/threonine kinase 11 Homo sapiens 14-18 28494141-9 2018 Collectively, functional OCT-expressing iPSC-MSCs responded to metformin by inducing an osteogenic effect in part mediated by the LKB1/AMPK pathway. Metformin 63-72 serine/threonine kinase 11 Homo sapiens 130-134 28775741-0 2017 STK11 rs2075604 Polymorphism Is Associated with Metformin Efficacy in Chinese Type 2 Diabetes Mellitus. Metformin 48-57 serine/threonine kinase 11 Homo sapiens 0-5 28775741-7 2017 The T allele in the STK11 rs2075604 had a 2.133 times great chance of responding to metformin treatment. Metformin 84-93 serine/threonine kinase 11 Homo sapiens 20-25 28775741-8 2017 In conclusion, this study suggested that the STK11 rs2075604 genetic polymorphism was significantly associated with metformin efficacy in Chinese T2DM patients and the carriers of the T allele may gain a better therapeutic metformin efficacy compared with the G allele. Metformin 116-125 serine/threonine kinase 11 Homo sapiens 45-50 28775741-8 2017 In conclusion, this study suggested that the STK11 rs2075604 genetic polymorphism was significantly associated with metformin efficacy in Chinese T2DM patients and the carriers of the T allele may gain a better therapeutic metformin efficacy compared with the G allele. Metformin 223-232 serine/threonine kinase 11 Homo sapiens 45-50 26847819-11 2016 These results provide evidence that the growth inhibition of metformin in NSCLC cells is mediated by LKB1-independent activation of AMPK, indicating that metformin may be a potential therapeutic agent for the treatment of human NSCLC. Metformin 61-70 serine/threonine kinase 11 Homo sapiens 101-105 26847819-11 2016 These results provide evidence that the growth inhibition of metformin in NSCLC cells is mediated by LKB1-independent activation of AMPK, indicating that metformin may be a potential therapeutic agent for the treatment of human NSCLC. Metformin 154-163 serine/threonine kinase 11 Homo sapiens 101-105 26847819-1 2016 Metformin, the most widely administered oral anti-diabetic therapeutic agent, exerts its glucose-lowering effect predominantly via liver kinase B1 (LKB1)-dependent activation of adenosine monophosphate-activated protein kinase (AMPK). Metformin 0-9 serine/threonine kinase 11 Homo sapiens 131-146 26847819-1 2016 Metformin, the most widely administered oral anti-diabetic therapeutic agent, exerts its glucose-lowering effect predominantly via liver kinase B1 (LKB1)-dependent activation of adenosine monophosphate-activated protein kinase (AMPK). Metformin 0-9 serine/threonine kinase 11 Homo sapiens 148-152 26717043-5 2016 Second, Metformin, a pharmacological AMPK activator and anti-diabetic drug, or ectopic expression of LKB1, diminished expression of Bmi-1 in cancer cells, an event that was reversed by silencing LKB1. Metformin 8-17 serine/threonine kinase 11 Homo sapiens 195-199 26893732-3 2016 The anticancer action of metformin involves the enhancement of phosphorylation of liver kinase B1, activation of adenosine monophosphate-activated protein kinase and inhibition of mammalian target of rapamycin, which reduces cell growth. Metformin 25-34 serine/threonine kinase 11 Homo sapiens 82-97 26740120-5 2016 Metformin influences various cellular pathways, including activation of the LKB1/AMPK pathway, inhibition of cell division, promotion of apoptosis and autophagy, down-regulation of circulating insulin, and activation of the immune system. Metformin 0-9 serine/threonine kinase 11 Homo sapiens 76-80 26745759-2 2016 Besides, the C allele of a SNP in the Lkb1 gene impedes the likelihood of ovulation in polycystic ovary syndrome (PCOS) in women treated with metformin, a known LKB1-AMPK activator. Metformin 142-151 serine/threonine kinase 11 Homo sapiens 38-42 26745759-2 2016 Besides, the C allele of a SNP in the Lkb1 gene impedes the likelihood of ovulation in polycystic ovary syndrome (PCOS) in women treated with metformin, a known LKB1-AMPK activator. Metformin 142-151 serine/threonine kinase 11 Homo sapiens 161-165 26673006-8 2016 CONCLUSIONS: Metformin potentiates the antitumor activity of MEK-Is in human LKB1-wild-type NSCLC cell lines, independently from the KRAS mutational status, through GLI1 downregulation and by reducing the NF-jB (p65)-mediated transcription of MMP-2 and MMP-9. Metformin 13-22 serine/threonine kinase 11 Homo sapiens 77-81 26673006-0 2016 Metformin increases antitumor activity of MEK inhibitors through GLI1 downregulation in LKB1 positive human NSCLC cancer cells. Metformin 0-9 serine/threonine kinase 11 Homo sapiens 88-92 26424816-1 2015 AMP-activated protein kinase (AMPK), an important downstream effector of the tumor suppressor liver kinase 1 (LKB1) and pharmacologic target of metformin, is well known to exert a preventive and inhibitory effect on tumorigenesis; however, its role in cancer progression and metastasis has not been well characterized. Metformin 144-153 serine/threonine kinase 11 Homo sapiens 110-114 26673006-2 2016 Our group recently has demonstrated that metformin and gefitinib are synergistic in LKB1-wild-type NSCLC cells. Metformin 41-50 serine/threonine kinase 11 Homo sapiens 84-88 26673006-4 2016 EXPERIMENTAL DESIGN: Since single agent metformin enhances proliferating signals through the RAS/RAF/MAPK pathway, and several MEK inhibitors (MEK-I) demonstrated clinical efficacy in combination with other agents in NSCLC, we tested the effects of metformin plus MEK-I (selumetinib or pimasertib) on proliferation, invasiveness, migration abilities in vitro and in vivo in LKB1 positive NSCLC models harboring KRAS wild type and mutated gene. Metformin 40-49 serine/threonine kinase 11 Homo sapiens 374-378 26424816-4 2015 The effect of metformin is dependent on the presence of LKB1. Metformin 14-23 serine/threonine kinase 11 Homo sapiens 56-60 26424816-6 2015 As a consequence, expression of genes downstream of Smad2/3, including plasminogen activator inhibitor-1, fibronectin, and connective tissue growth factor, was suppressed by metformin in a LKB1-dependent fashion. Metformin 174-183 serine/threonine kinase 11 Homo sapiens 189-193 26424816-7 2015 In addition, metformin blocked TGF-beta-induced inteleukin-6 expression through both LKB1-dependent and -independent mechanisms. Metformin 13-22 serine/threonine kinase 11 Homo sapiens 85-89 25538235-5 2015 In the current study, we find that low concentrations of metformin promote the formation of the AMPK alphabetagamma complex, resulting in an increase in net phosphorylation of the AMPK alpha catalytic subunit at Thr-172 by augmenting phosphorylation by LKB1 and antagonizing dephosphorylation by PP2C. Metformin 57-66 serine/threonine kinase 11 Homo sapiens 253-257 26383681-7 2015 Interestingly, metformin may enhance radiation response specifically in certain genetic backgrounds, such as in cells with loss of the tumor suppressors p53 and LKB1, giving rise to a therapeutic ratio and potential predictive biomarkers. Metformin 15-24 serine/threonine kinase 11 Homo sapiens 161-165 25734181-5 2015 Metformin, an antidiabetic drug, is effective for endometrial cancer through inhibition of the PI3K-Akt-mTOR pathway by activating LKB1-AMPK and reduction of insulin and insulin-like growth factor-1 due to AMPK activation. Metformin 0-9 serine/threonine kinase 11 Homo sapiens 131-135 25607951-14 2015 These findings--albeit limited to a single case--suggest that tumors lacking LKB1 expression and/or endowed with an highly glycolytic phenotype might develop large necrotic areas following combined treatment with metformin plus bevacizumab. Metformin 213-222 serine/threonine kinase 11 Homo sapiens 77-81 24862830-3 2015 Metformin decreases hepatic glucose production via a mechanism requiring liver kinase B1, which controls the metabolic checkpoint, AMP-activated protein kinase-mammalian target of rapamycin and neoglucogenic genes. Metformin 0-9 serine/threonine kinase 11 Homo sapiens 73-88 23526220-1 2013 Metformin has been used as first-line treatment in patients with type 2 diabetes, and is reported to reduce cancer risk and progression by activating the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway. Metformin 0-9 serine/threonine kinase 11 Homo sapiens 154-169 24473757-5 2013 CONCLUSIONS: Metformin, due to its independent effects on liver kinase B1, had antiproliferative effects on the NCI-H460 cell line. Metformin 13-22 serine/threonine kinase 11 Homo sapiens 58-73 24916949-5 2014 Re-expression of LKB-1 in HeLa-S3 cells restored the growth inhibitory effect of metformin, indicating a requirement for LKB-1 in metformin-induced growth inhibition. Metformin 81-90 serine/threonine kinase 11 Homo sapiens 17-22 24916949-5 2014 Re-expression of LKB-1 in HeLa-S3 cells restored the growth inhibitory effect of metformin, indicating a requirement for LKB-1 in metformin-induced growth inhibition. Metformin 130-139 serine/threonine kinase 11 Homo sapiens 17-22 24504677-3 2014 The biomolecular characteristics of tumors, such as appropriate expression of organic cation transporters or genetic alterations including p53, K-ras, LKB1, and PI3K may impact metformin"s anticancer efficiency. Metformin 177-186 serine/threonine kinase 11 Homo sapiens 151-155 25329671-4 2014 Activation of LKB1/AMPK pathway and cancer stem cell destruction along with cell cycle arrest and apoptosis induction are the proposed mechanisms of anticancer potential of metformin. Metformin 173-182 serine/threonine kinase 11 Homo sapiens 14-18 24750786-3 2014 Metformin exerts anticancer effects by primarily blocking the pivotal LKB1/AMPK/mTOR/S6K1 pathway-dependent cell growth, induces selective lethal effects on GSC by impairing the GSC-initiating spherogenesis and inhibits the proliferation of CD133+ cells, while having a low or null effect on differentiated glioblastoma cells and normal human stem cells. Metformin 0-9 serine/threonine kinase 11 Homo sapiens 70-74 23526220-1 2013 Metformin has been used as first-line treatment in patients with type 2 diabetes, and is reported to reduce cancer risk and progression by activating the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway. Metformin 0-9 serine/threonine kinase 11 Homo sapiens 171-175 23526220-11 2013 This is the first study to demonstrate that metformin suppresses STAT3 activation via LKB1-AMPK-mTOR-independent but ROS-related and autocrine IL-6 production-related pathways. Metformin 44-53 serine/threonine kinase 11 Homo sapiens 86-90 23695170-0 2013 Synergistic effects of metformin treatment in combination with gefitinib, a selective EGFR tyrosine kinase inhibitor, in LKB1 wild-type NSCLC cell lines. Metformin 23-32 serine/threonine kinase 11 Homo sapiens 121-125 23695170-4 2013 RESULTS: The combination of metformin with gefitinib induced a strong antiproliferative and proapoptotic effect in NSCLC cell lines that harbored wild-type LKB1 gene. Metformin 28-37 serine/threonine kinase 11 Homo sapiens 156-160 23695170-7 2013 CONCLUSIONS: Metformin and gefitinib are synergistic in LKB1 wild-type NSCLC cells. Metformin 13-22 serine/threonine kinase 11 Homo sapiens 56-60 23612973-2 2013 In a previous study, we demonstrated that phosphorylation of Ser-428/431 (in LKB1(L)) by protein kinase Czeta (PKCzeta) was essential for LKB1-mediated activation of AMP-activated protein kinase (AMPK) in response to oxidants or metformin. Metformin 229-238 serine/threonine kinase 11 Homo sapiens 77-81 22773548-9 2013 Cell line studies showed that metformin inhibits hepatocyte proliferation and induces cell cycle arrest at G0/G1 phase via AMP-activated protein kinase and its upstream kinase LKB1 to upregulate p21/Cip1 and p27/Kip1 and downregulate cyclin D1 in a dose-dependent manner, but independent of p53. Metformin 30-39 serine/threonine kinase 11 Homo sapiens 176-180 23612973-2 2013 In a previous study, we demonstrated that phosphorylation of Ser-428/431 (in LKB1(L)) by protein kinase Czeta (PKCzeta) was essential for LKB1-mediated activation of AMP-activated protein kinase (AMPK) in response to oxidants or metformin. Metformin 229-238 serine/threonine kinase 11 Homo sapiens 138-142 23612973-8 2013 PKCzeta-dependent phosphorylation of Ser-399 triggered nucleocytoplasmic translocation of LKB1(S) in response to metformin or peroxynitrite treatment. Metformin 113-122 serine/threonine kinase 11 Homo sapiens 90-94 23577667-9 2013 Treatment of HTLV-1 transformed cells with metformin led to LKB1/SIK1 activation, reduction in Tax expression, and inhibition of cell proliferation. Metformin 43-52 serine/threonine kinase 11 Homo sapiens 60-64 22735790-0 2012 Metformin impairs the growth of liver kinase B1-intact cervical cancer cells. Metformin 0-9 serine/threonine kinase 11 Homo sapiens 32-47 23991948-2 2013 Besides the discovery of somatic mutations in the LKB1 gene in certain type of cancers, a critical emerging point was that the LKB1/AMPK axis remains generally functional and could be stimulated by pharmacological molecules such as metformin in cancer cells. Metformin 232-241 serine/threonine kinase 11 Homo sapiens 50-54 23991948-2 2013 Besides the discovery of somatic mutations in the LKB1 gene in certain type of cancers, a critical emerging point was that the LKB1/AMPK axis remains generally functional and could be stimulated by pharmacological molecules such as metformin in cancer cells. Metformin 232-241 serine/threonine kinase 11 Homo sapiens 127-131 22735790-3 2012 The present study aimed to determine the role of liver kinase B1 (LKB1) in the response of cervical cancer cells to metformin. Metformin 116-125 serine/threonine kinase 11 Homo sapiens 49-64 22735790-3 2012 The present study aimed to determine the role of liver kinase B1 (LKB1) in the response of cervical cancer cells to metformin. Metformin 116-125 serine/threonine kinase 11 Homo sapiens 66-70 22735790-7 2012 Analyzing the expression status and the integrity of LKB1-AMPK-mTOR signaling, we found that cervical cancer cells sensitive to metformin were LKB1 intact and exerted an integral AMPK-mTOR signaling response after the treatment. Metformin 128-137 serine/threonine kinase 11 Homo sapiens 53-57 22735790-7 2012 Analyzing the expression status and the integrity of LKB1-AMPK-mTOR signaling, we found that cervical cancer cells sensitive to metformin were LKB1 intact and exerted an integral AMPK-mTOR signaling response after the treatment. Metformin 128-137 serine/threonine kinase 11 Homo sapiens 143-147 22735790-8 2012 Ectopic expression of LKB1 with stable transduction system or inducible expression construct in endogenous LKB1 deficient cells improved the activation of AMPK, promoted the inhibition of mTOR, and prompted the sensitivity of cells to metformin. Metformin 235-244 serine/threonine kinase 11 Homo sapiens 22-26 22735790-8 2012 Ectopic expression of LKB1 with stable transduction system or inducible expression construct in endogenous LKB1 deficient cells improved the activation of AMPK, promoted the inhibition of mTOR, and prompted the sensitivity of cells to metformin. Metformin 235-244 serine/threonine kinase 11 Homo sapiens 107-111 22735790-9 2012 In contrast, knock-down of LKB1 compromised cellular response to metformin. Metformin 65-74 serine/threonine kinase 11 Homo sapiens 27-31 22735790-10 2012 Our further investigation demonstrated that metformin could induce both apoptosis and autophagy in cervical cancer cells when LKB1 is expressed. Metformin 44-53 serine/threonine kinase 11 Homo sapiens 126-130 22735790-11 2012 CONCLUSIONS: Metformin is a potential drug for the treatment of cervical cancers, in particular to those with intact LKB1 expression. Metformin 13-22 serine/threonine kinase 11 Homo sapiens 117-121 22686561-4 2012 A critical point is that the LKB1/AMPK network remains functional in a wide range of cancers and could be stimulated by drugs, such as N,N-dimethylimidodicarbonimidic diamide (metformin) or 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR). Metformin 135-174 serine/threonine kinase 11 Homo sapiens 29-33 22686561-4 2012 A critical point is that the LKB1/AMPK network remains functional in a wide range of cancers and could be stimulated by drugs, such as N,N-dimethylimidodicarbonimidic diamide (metformin) or 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR). Metformin 176-185 serine/threonine kinase 11 Homo sapiens 29-33 21301998-2 2012 Several potential mechanisms have been suggested for the ability of metformin to suppress cancer growth in vitro and vivo: (1) activation of LKB1/AMPK pathway, (2) induction of cell cycle arrest and/or apoptosis, (3) inhibition of protein synthesis, (4) reduction in circulating insulin levels, (5) inhibition of the unfolded protein response (UPR), (6) activation of the immune system, and (7) eradication of cancer stem cells. Metformin 68-77 serine/threonine kinase 11 Homo sapiens 141-145 21572254-2 2011 Besides the discovery of somatic mutations in the LKB1 gene in certain type of cancers, a critical emerging point was that the LKB1/AMPK axis remains generally functional and could be stimulated by pharmacological molecules such as metformin in cancer cells. Metformin 232-241 serine/threonine kinase 11 Homo sapiens 50-54 21968881-4 2012 Here, we have explored the therapeutic potential of the anti-diabetic drug, metformin (an LKB1/AMPK activator), against both T-cell acute lymphoblastic leukemia (T-ALL) cell lines and primary samples from T-ALL patients displaying mTORC1 activation. Metformin 76-85 serine/threonine kinase 11 Homo sapiens 90-94 21968881-10 2012 In conclusion, metformin displayed a remarkable anti-leukemic activity, which emphasizes future development of LKB1/AMPK activators as clinical candidates for therapy in T-ALL. Metformin 15-24 serine/threonine kinase 11 Homo sapiens 111-115 21631893-6 2011 The major molecular targets of metformin are the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) signaling and mammalian target of rapamycin (mTOR) pathways, which are central in the regulation of cellular energy homeostasis and play a crucial role in the control of cell division and cell proliferation. Metformin 31-40 serine/threonine kinase 11 Homo sapiens 49-64 21631893-6 2011 The major molecular targets of metformin are the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) signaling and mammalian target of rapamycin (mTOR) pathways, which are central in the regulation of cellular energy homeostasis and play a crucial role in the control of cell division and cell proliferation. Metformin 31-40 serine/threonine kinase 11 Homo sapiens 66-70 21835890-5 2011 Interestingly, we found that metformin also induces LKB1 cytosolic translocation, but the stimulation is independent of APPL1 and the PP2A-PKCzeta pathway. Metformin 29-38 serine/threonine kinase 11 Homo sapiens 52-56 23029387-8 2012 In LKB1 deficient (A549, HeLa) and expressing (SCC9, SCC25) cell lines, metformin enhanced gefitinib cytotoxicity only in LKB1 expressing cell lines while both groups showed synergistic cytotoxic effects with lovastatin treatments. Metformin 72-81 serine/threonine kinase 11 Homo sapiens 3-7 23029387-8 2012 In LKB1 deficient (A549, HeLa) and expressing (SCC9, SCC25) cell lines, metformin enhanced gefitinib cytotoxicity only in LKB1 expressing cell lines while both groups showed synergistic cytotoxic effects with lovastatin treatments. Metformin 72-81 serine/threonine kinase 11 Homo sapiens 122-126 21572254-2 2011 Besides the discovery of somatic mutations in the LKB1 gene in certain type of cancers, a critical emerging point was that the LKB1/AMPK axis remains generally functional and could be stimulated by pharmacological molecules such as metformin in cancer cells. Metformin 232-241 serine/threonine kinase 11 Homo sapiens 127-131 21572254-4 2011 Further basic research work should be conducted to elucidate the molecular targets of LKB1/AMPK responsible for its anti-tumor activity in parallel of conducting clinical trials using metformin, AICAR or new AMPK activating agents to explore the potential of the LKB1/AMPK signaling pathway as a new target for anticancer drug development. Metformin 184-193 serine/threonine kinase 11 Homo sapiens 86-90 19520843-2 2009 Here we show that in muscle cells adiponectin and metformin induce AMPK activation by promoting APPL1-dependent LKB1 cytosolic translocation. Metformin 50-59 serine/threonine kinase 11 Homo sapiens 112-116 21123367-4 2011 We found that in LKB1-null A549 lung adenocarcinoma cells, an AMPK activator, metformin, failed to block the nuclear export of PTEN, and the reintroduction of functional LKB1 into these cells restored the metformin-mediated inhibition of the nuclear export of PTEN. Metformin 205-214 serine/threonine kinase 11 Homo sapiens 170-174 21123367-6 2011 Although the nuclear export of PTEN is blocked by metformin in MCF-7 breast cancer cells carrying wild-type LKB1, this inhibition could not be reversed by an AMPK inhibitor, suggesting that LKB1 could regulate the nuclear export of PTEN by bypassing AMPK alpha1/2. Metformin 50-59 serine/threonine kinase 11 Homo sapiens 190-194 21123367-8 2011 However, metformin was still able to induce the LKB1-mediated inhibition of the nuclear export of PTEN in these cells. Metformin 9-18 serine/threonine kinase 11 Homo sapiens 48-52 21349801-6 2011 Concomitantly, metformin induces activation of LKB1 (serine/threonine kinase 11), a tumor suppressor gene, which is required for the phosphorylation and activation of AMPK. Metformin 15-24 serine/threonine kinase 11 Homo sapiens 47-51 21349801-6 2011 Concomitantly, metformin induces activation of LKB1 (serine/threonine kinase 11), a tumor suppressor gene, which is required for the phosphorylation and activation of AMPK. Metformin 15-24 serine/threonine kinase 11 Homo sapiens 53-79 20300828-6 2010 Interestingly, metformin also causes a significant increase in LKB1 protein expression and promoter activity, thereby providing for the first time an additional mechanism by which metformin activates AMPK. Metformin 15-24 serine/threonine kinase 11 Homo sapiens 63-67 20300828-6 2010 Interestingly, metformin also causes a significant increase in LKB1 protein expression and promoter activity, thereby providing for the first time an additional mechanism by which metformin activates AMPK. Metformin 180-189 serine/threonine kinase 11 Homo sapiens 63-67 19858366-0 2009 LKB1 and mammalian target of rapamycin as predictive factors for the anticancer efficacy of metformin. Metformin 92-101 serine/threonine kinase 11 Homo sapiens 0-4 18681789-1 2008 Metformin, ovulation and polymorphism of the STK11 gene in polycystic ovary syndrome. Metformin 0-9 serine/threonine kinase 11 Homo sapiens 45-50 18681789-17 2008 The C allele of a SNP in the STK11 gene was associated with a significantly decreased chance of ovulation in polycystic ovary syndrome women treated with metformin. Metformin 154-163 serine/threonine kinase 11 Homo sapiens 29-34 34607979-9 2021 Consistently, the overexpression of LKB1 in HeLa cancer cells prevented metformin-triggered apoptosis while LKB1 knockdown significantly increased apoptosis in HEC-1-A and KLE cancer cells. Metformin 72-81 serine/threonine kinase 11 Homo sapiens 36-40 18000088-7 2008 RESULTS: We found that the C allele of a single nucleotide polymorphism in the STK11 gene (expressed in liver; also known as LKB1) was associated with a significantly decreased chance of ovulation in PCOS women treated with metformin. Metformin 224-233 serine/threonine kinase 11 Homo sapiens 79-84 18000088-7 2008 RESULTS: We found that the C allele of a single nucleotide polymorphism in the STK11 gene (expressed in liver; also known as LKB1) was associated with a significantly decreased chance of ovulation in PCOS women treated with metformin. Metformin 224-233 serine/threonine kinase 11 Homo sapiens 125-129 18000088-11 2008 CONCLUSIONS: We have demonstrated that a polymorphism in STK11, a kinase gene expressed in liver and implicated in metformin action, is associated with ovulatory response to treatment with metformin alone in a prospective randomized trial. Metformin 115-124 serine/threonine kinase 11 Homo sapiens 57-62 18000088-11 2008 CONCLUSIONS: We have demonstrated that a polymorphism in STK11, a kinase gene expressed in liver and implicated in metformin action, is associated with ovulatory response to treatment with metformin alone in a prospective randomized trial. Metformin 189-198 serine/threonine kinase 11 Homo sapiens 57-62 18250273-3 2008 METHODS AND RESULTS: Exposure of human umbilical vein endothelial cells or bovine aortic endothelial cells to metformin significantly increased AMPK activity and the phosphorylation of both AMPK at Thr172 and LKB1 at Ser428, an AMPK kinase, which was paralleled by increased activation of protein kinase C (PKC)-zeta, as evidenced by increased activity, phosphorylation (Thr410/403), and nuclear translocation of PKC-zeta. Metformin 110-119 serine/threonine kinase 11 Homo sapiens 209-213 18250273-4 2008 Consistently, either pharmacological or genetic inhibition of PKC-zeta ablated metformin-enhanced phosphorylation of both AMPK-Thr172 and LKB1-Ser428, suggesting that PKC-zeta might act as an upstream kinase for LKB1. Metformin 79-88 serine/threonine kinase 11 Homo sapiens 138-142 18250273-4 2008 Consistently, either pharmacological or genetic inhibition of PKC-zeta ablated metformin-enhanced phosphorylation of both AMPK-Thr172 and LKB1-Ser428, suggesting that PKC-zeta might act as an upstream kinase for LKB1. Metformin 79-88 serine/threonine kinase 11 Homo sapiens 212-216 18250273-5 2008 Furthermore, adenoviral overexpression of LKB1 kinase-dead mutants abolished but LKB1 wild-type overexpression enhanced the effects of metformin on AMPK in bovine aortic endothelial cells. Metformin 135-144 serine/threonine kinase 11 Homo sapiens 81-85 18250273-6 2008 In addition, metformin increased the phosphorylation and nuclear export of LKB1 into the cytosols as well as the association of AMPK with LKB1 in bovine aortic endothelial cells. Metformin 13-22 serine/threonine kinase 11 Homo sapiens 75-79 18250273-6 2008 In addition, metformin increased the phosphorylation and nuclear export of LKB1 into the cytosols as well as the association of AMPK with LKB1 in bovine aortic endothelial cells. Metformin 13-22 serine/threonine kinase 11 Homo sapiens 138-142 18250273-7 2008 Similarly, overexpression of LKB1 wild-type but not LKB1 S428A mutants (serine replaced by alanine) restored the effects of metformin on AMPK in LKB1-deficient HeLa-S3 cells, suggesting that Ser428 phosphorylation of LKB1 is required for metformin-enhanced AMPK activation. Metformin 124-133 serine/threonine kinase 11 Homo sapiens 29-33 18250273-7 2008 Similarly, overexpression of LKB1 wild-type but not LKB1 S428A mutants (serine replaced by alanine) restored the effects of metformin on AMPK in LKB1-deficient HeLa-S3 cells, suggesting that Ser428 phosphorylation of LKB1 is required for metformin-enhanced AMPK activation. Metformin 238-247 serine/threonine kinase 11 Homo sapiens 29-33 18250273-8 2008 Moreover, LKB1 S428A, like kinase-dead LKB1 D194A, abolished metformin-enhanced LKB1 translocation as well as the association of LKB1 with AMPK in HeLa-S3 cells. Metformin 61-70 serine/threonine kinase 11 Homo sapiens 10-14 18250273-8 2008 Moreover, LKB1 S428A, like kinase-dead LKB1 D194A, abolished metformin-enhanced LKB1 translocation as well as the association of LKB1 with AMPK in HeLa-S3 cells. Metformin 61-70 serine/threonine kinase 11 Homo sapiens 39-43 18250273-8 2008 Moreover, LKB1 S428A, like kinase-dead LKB1 D194A, abolished metformin-enhanced LKB1 translocation as well as the association of LKB1 with AMPK in HeLa-S3 cells. Metformin 61-70 serine/threonine kinase 11 Homo sapiens 39-43 18250273-8 2008 Moreover, LKB1 S428A, like kinase-dead LKB1 D194A, abolished metformin-enhanced LKB1 translocation as well as the association of LKB1 with AMPK in HeLa-S3 cells. Metformin 61-70 serine/threonine kinase 11 Homo sapiens 39-43 18250273-9 2008 Finally, inhibition of PKC-zeta abolished metformin-enhanced coimmunoprecipitation of LKB1 with both AMPKalpha1 and AMPKalpha2. Metformin 42-51 serine/threonine kinase 11 Homo sapiens 86-90 16530014-4 2006 Importantly, the absence of LKB1 in the liver abolishes the effect of lowering glucose level caused by metformin, a drug that is widely used for the treatment of type 2 diabetes. Metformin 103-112 serine/threonine kinase 11 Homo sapiens 28-32 20668229-2 2010 We show in our current study that the LKB1/AMPK/TSC tumor suppressor axis is functional in AML and can be activated by the biguanide molecule metformin, resulting in a specific inhibition of mammalian target of rapamycin (mTOR) catalytic activity. Metformin 142-151 serine/threonine kinase 11 Homo sapiens 38-42 34920124-8 2022 When treated with metformin/LKB1, both SLCO1B3 expression and intracellular PTX concentration have increased. Metformin 18-27 serine/threonine kinase 11 Homo sapiens 28-32 34927008-7 2021 Metformin activates the LKB1/AMPK pathway to interact with several intracellular signaling pathways and molecular mechanisms. Metformin 0-9 serine/threonine kinase 11 Homo sapiens 24-28 18250273-0 2008 Phosphorylation of LKB1 at serine 428 by protein kinase C-zeta is required for metformin-enhanced activation of the AMP-activated protein kinase in endothelial cells. Metformin 79-88 serine/threonine kinase 11 Homo sapiens 19-23 16354680-7 2006 Knockdown of Raptor as well as activators of the LKB1/AMPK pathway, such as the widely used antidiabetic compound metformin, suppress IRS-1 Ser636/639 phosphorylation and reverse mTOR-mediated inhibition on PI3-kinase/Akt signaling. Metformin 114-123 serine/threonine kinase 11 Homo sapiens 49-53 20357370-0 2010 A single nucleotide polymorphism in STK11 influences insulin sensitivity and metformin efficacy in hyperinsulinemic girls with androgen excess. Metformin 77-86 serine/threonine kinase 11 Homo sapiens 36-41 20357370-2 2010 We tested the hypothesis that a gene variant in STK11 contributes to variation in insulin sensitivity and metformin efficacy. Metformin 106-115 serine/threonine kinase 11 Homo sapiens 48-53 20357370-9 2010 The response to metformin differed by STK11 genotype: GG homozygotes (n = 24) had robust metabolic improvements, GC heterozygotes (n = 38) had intermediate responses, and CC homozygotes (n = 23) had almost no response. Metformin 16-25 serine/threonine kinase 11 Homo sapiens 38-43 20357370-11 2010 CONCLUSIONS: In hyperinsulinemic girls with androgen excess, the STK11 rs8111699 SNP influences insulin sensitivity and metformin efficacy, so that the girls with the least favorable endocrine-metabolic profile improve most with metformin therapy. Metformin 120-129 serine/threonine kinase 11 Homo sapiens 65-70 20357370-11 2010 CONCLUSIONS: In hyperinsulinemic girls with androgen excess, the STK11 rs8111699 SNP influences insulin sensitivity and metformin efficacy, so that the girls with the least favorable endocrine-metabolic profile improve most with metformin therapy. Metformin 229-238 serine/threonine kinase 11 Homo sapiens 65-70 34607979-10 2021 Taken together, these findings indicate an underlying biological/physiological molecular function specifically for metformin-triggered apoptosis dependent on the presence of the LKB1 gene in tumorigenesis. Metformin 115-124 serine/threonine kinase 11 Homo sapiens 178-182 35281267-0 2022 Metformin Combining PD-1 Inhibitor Enhanced Anti-Tumor Efficacy in STK11 Mutant Lung Cancer Through AXIN-1-Dependent Inhibition of STING Ubiquitination. Metformin 0-9 serine/threonine kinase 11 Homo sapiens 67-72 35281267-2 2022 The glucose-lowering drug metformin exerted anti-cancer effect and enhanced efficacy of chemotherapy in NSCLC with KRAS/STK11 co-mutation, yet it is unknown whether metformin may enhance ICI efficacy in STK11 mutant NSCLC. Metformin 26-35 serine/threonine kinase 11 Homo sapiens 120-125 35281267-13 2022 Conclusion: Metformin combining PD-1 inhibitor enhanced anti-tumor efficacy in STK11 mutant lung cancer through inhibition of RNF5-mediated K48-linked ubiquitination of STING, which was dependent on AXIN-1. Metformin 12-21 serine/threonine kinase 11 Homo sapiens 79-84