PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 33788730-3 2021 MATERIALS AND METHODS: Metformin with trametinib and paclitaxel was tested for effects on cell viability, signaling molecules in MAPK and mTOR pathways, factors involved in epithelial-mesenchymal transition (EMT), and cell motility. Metformin 23-32 mitogen-activated protein kinase 1 Homo sapiens 129-133 33524789-6 2021 First, many studies showed that metformin could induce autophagy via a number of signaling pathways, including AMPK-related signaling pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3beta, and TRIB3. Metformin 32-41 mitogen-activated protein kinase 1 Homo sapiens 255-259 33524789-6 2021 First, many studies showed that metformin could induce autophagy via a number of signaling pathways, including AMPK-related signaling pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3beta, and TRIB3. Metformin 32-41 mitogen-activated protein kinase 1 Homo sapiens 260-263 33788730-4 2021 RESULTS: The combination of metformin with trametinib and paclitaxel showed differential growth inhibitory effects; synergistic effects were observed in a cell line in which metformin suppresses ERK activity, whereas the combination showed antagonistic effects in a cell line with metformin-induced ERK activation. Metformin 28-37 mitogen-activated protein kinase 1 Homo sapiens 195-198 33788730-4 2021 RESULTS: The combination of metformin with trametinib and paclitaxel showed differential growth inhibitory effects; synergistic effects were observed in a cell line in which metformin suppresses ERK activity, whereas the combination showed antagonistic effects in a cell line with metformin-induced ERK activation. Metformin 28-37 mitogen-activated protein kinase 1 Homo sapiens 299-302 33126710-10 2020 In agreement with the changes on mitochondrial morphology, the ERK-Akt signal axis dependent Drp-1 phosphorylation at S616 (an index of mitochondrial fission) under NaIO3 treatment was blocked by A769662, but not by metformin. Metformin 216-225 mitogen-activated protein kinase 1 Homo sapiens 63-66 33652909-9 2021 In addition, metformin activated the pathways of AMPKalpha and MEK/ERK to phosphorylate p27(Thr198) and reduce mTOR phosphorylation in cells. Metformin 13-22 mitogen-activated protein kinase 1 Homo sapiens 67-70 32951587-5 2021 In this review, we summarize the chemosensitization effects of metformin and focus primarily on its molecular mechanisms in enhancing the sensitivity of multiple chemotherapeutic drugs, through targeting of mTOR, ERK/P70S6K, NF-kappaB/HIF-1alpha, and mitogenactivated protein kinase (MAPK) signaling pathways, as well as by down-regulating the expression of CSC genes and pyruvate kinase isoenzyme M2 (PKM2). Metformin 63-72 mitogen-activated protein kinase 1 Homo sapiens 213-216 33489797-10 2020 Mechanistically, metformin extensively dephosphorylates Nrf2 by attenuating the interaction between Nrf2 and extracellular signal-regulated kinases 1/2 (ERK1/2), which then restores its polyubiquitination and accelerates its proteasomal degradation. Metformin 17-26 mitogen-activated protein kinase 1 Homo sapiens 109-151 32734128-3 2020 Metformin-induced activation of ERK is therapeutically important, since metformin could enhance cell proliferation through RAS/RAF/MEK/ERK pathway and lead to impairment of its anticancer activity suppressing PI3K/AKT/mTOR pathway, requiring blockade of both signaling pathways for more efficient antitumor effect. Metformin 72-81 mitogen-activated protein kinase 1 Homo sapiens 32-35 33014814-0 2020 Metformin Overcomes Acquired Resistance to EGFR TKIs in EGFR-Mutant Lung Cancer via AMPK/ERK/NF-kappaB Signaling Pathway. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 89-92 33014814-11 2020 Mechanistically, those effects of metformin were associated with activation of AMPK, resulting in the inhibition of downstream ERK/NF-kappaB signaling. Metformin 34-43 mitogen-activated protein kinase 1 Homo sapiens 127-130 32248666-13 2020 The AMPK/Erk signaling pathway experiments revealed that the upregulation of Bcl-2 induced by insulin through Erk phosphorylation was inhibited by metformin and that such inhibition could be mitigated by the inhibition of AMPK. Metformin 147-156 mitogen-activated protein kinase 1 Homo sapiens 9-12 32248666-13 2020 The AMPK/Erk signaling pathway experiments revealed that the upregulation of Bcl-2 induced by insulin through Erk phosphorylation was inhibited by metformin and that such inhibition could be mitigated by the inhibition of AMPK. Metformin 147-156 mitogen-activated protein kinase 1 Homo sapiens 110-113 32734128-2 2020 In NSCLC cells, metformin suppresses PI3K/AKT/mTOR signaling pathway, but effect of metformin on RAS/ RAF/MEK/ERK signaling pathway is controversial; several studies showed the inhibition of ERK activity, while others demonstrated the activation of ERK in response to metformin exposure. Metformin 84-93 mitogen-activated protein kinase 1 Homo sapiens 110-113 32734128-2 2020 In NSCLC cells, metformin suppresses PI3K/AKT/mTOR signaling pathway, but effect of metformin on RAS/ RAF/MEK/ERK signaling pathway is controversial; several studies showed the inhibition of ERK activity, while others demonstrated the activation of ERK in response to metformin exposure. Metformin 84-93 mitogen-activated protein kinase 1 Homo sapiens 110-113 32734128-3 2020 Metformin-induced activation of ERK is therapeutically important, since metformin could enhance cell proliferation through RAS/RAF/MEK/ERK pathway and lead to impairment of its anticancer activity suppressing PI3K/AKT/mTOR pathway, requiring blockade of both signaling pathways for more efficient antitumor effect. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 32-35 32734128-3 2020 Metformin-induced activation of ERK is therapeutically important, since metformin could enhance cell proliferation through RAS/RAF/MEK/ERK pathway and lead to impairment of its anticancer activity suppressing PI3K/AKT/mTOR pathway, requiring blockade of both signaling pathways for more efficient antitumor effect. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 135-138 32734128-3 2020 Metformin-induced activation of ERK is therapeutically important, since metformin could enhance cell proliferation through RAS/RAF/MEK/ERK pathway and lead to impairment of its anticancer activity suppressing PI3K/AKT/mTOR pathway, requiring blockade of both signaling pathways for more efficient antitumor effect. Metformin 72-81 mitogen-activated protein kinase 1 Homo sapiens 135-138 32734128-5 2020 We show that metformin alone blocks PI3K/AKT/mTOR signaling pathway but induces the activation and phosphorylation of ERK. Metformin 13-22 mitogen-activated protein kinase 1 Homo sapiens 118-121 32734128-7 2020 These findings suggest that the efficacy of metformin and trametinib combination therapy may depend on the alteration of ERK activity induced by metformin and specific cellular context of cancer cells. Metformin 44-53 mitogen-activated protein kinase 1 Homo sapiens 121-124 32734128-7 2020 These findings suggest that the efficacy of metformin and trametinib combination therapy may depend on the alteration of ERK activity induced by metformin and specific cellular context of cancer cells. Metformin 145-154 mitogen-activated protein kinase 1 Homo sapiens 121-124 31348945-0 2019 Metformin reduces fibrosis factors in insulin resistant and hypertrophied adipocyte via integrin/ERK, collagen VI, apoptosis, and necrosis reduction. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 97-100 31789625-12 2020 Our discovery revealed that metformin, via increasing the expression of microRNA-7 mediated by AMPK, regulates the AKT/mTOR, MAPK/Erk, and NF-kappaB signaling pathways, thereby suppressing A549 cell growth, migration, and invasion. Metformin 28-37 mitogen-activated protein kinase 1 Homo sapiens 130-133 31886264-7 2019 Metformin phosphorylates extracellular signal-regulated kinase (ERK), stimulates endothelial and inducible nitric oxide synthases (e/iNOS), inhibits the GSK3beta/Wnt/beta-catenin pathway, and promotes osteogenic differentiation of osteoblasts. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 25-62 31886264-7 2019 Metformin phosphorylates extracellular signal-regulated kinase (ERK), stimulates endothelial and inducible nitric oxide synthases (e/iNOS), inhibits the GSK3beta/Wnt/beta-catenin pathway, and promotes osteogenic differentiation of osteoblasts. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 64-67 31348945-8 2019 Metformin caused reduction of activity of integrin/ERK pathway in Metformin treated insulin resistant and hypertrophied adipocytes compared to untreated group. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 51-54 31348945-8 2019 Metformin caused reduction of activity of integrin/ERK pathway in Metformin treated insulin resistant and hypertrophied adipocytes compared to untreated group. Metformin 66-75 mitogen-activated protein kinase 1 Homo sapiens 51-54 30153063-9 2019 Metformin-flutamide treatment upregulated hepatic and intestinal insulin signaling, including insulin receptor, MAPK1, and AKT2. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 112-117 31321352-3 2019 Metformin suppresses the mammalian target of rapamycin (mTOR) and our previous study showed that it also inhibits the activity of extracellular signal-regulated kinase (ERK). Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 130-167 31321352-3 2019 Metformin suppresses the mammalian target of rapamycin (mTOR) and our previous study showed that it also inhibits the activity of extracellular signal-regulated kinase (ERK). Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 169-172 30551411-12 2019 Metformin alleviated EP-triggered p38 MAPK inactivation and PGR (PGRA and PGRB) expression. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 34-37 30551411-14 2019 CONCLUSION: Metformin alleviated EP-induced decidualization of endometrial stromal cells by modulating secretion of multiple cytokines, inhibiting expression of MMP-2 and MMP-9, activating p38-MAPK signaling and reducing PGR expression, providing a deep insight into the molecular basis of metfromin therapy for PCOS patients. Metformin 12-21 mitogen-activated protein kinase 1 Homo sapiens 189-192 30551515-7 2019 The mechanism of metformin and binimetinib synergy in melanoma cells was associated with increased activation of p-AMPKalpha and decreased p-ERK, but not with alterations in p-mTOR. Metformin 17-26 mitogen-activated protein kinase 1 Homo sapiens 141-144 29630425-8 2018 RESULTS: Metformin suppressed LPS-induced IP-10 and MCP-1 production as well as LPS-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38, extracellular signal-regulated kinase (ERK), and nuclear factor-kappa B (NF-kappaB). Metformin 9-18 mitogen-activated protein kinase 1 Homo sapiens 147-184 29630425-8 2018 RESULTS: Metformin suppressed LPS-induced IP-10 and MCP-1 production as well as LPS-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38, extracellular signal-regulated kinase (ERK), and nuclear factor-kappa B (NF-kappaB). Metformin 9-18 mitogen-activated protein kinase 1 Homo sapiens 186-189 29630425-11 2018 Suppressive effects of metformin on IP-10 production might be attributed at least partially to the JNK, p38, ERK, and NF-kappaB pathways as well as to epigenetic regulation through the acetylation of histones H3 and H4. Metformin 23-32 mitogen-activated protein kinase 1 Homo sapiens 104-107 29630425-11 2018 Suppressive effects of metformin on IP-10 production might be attributed at least partially to the JNK, p38, ERK, and NF-kappaB pathways as well as to epigenetic regulation through the acetylation of histones H3 and H4. Metformin 23-32 mitogen-activated protein kinase 1 Homo sapiens 109-112 30023463-4 2018 We previously reported that metformin inhibits the phosphorylation of ERK and BEZ235, a dual inhibitor of PI3K and mTOR, has anti-tumor activity against HCT15 CRC cells harboring mutations of KRAS and PIK3CA. Metformin 28-37 mitogen-activated protein kinase 1 Homo sapiens 70-73 30333878-7 2018 Metformin inhibited the Akt and extracellular signal-regulated kinase (ERK)1/2 pathways in A549 cells and activated the p38 MAPK and c-Jun N-terminal kinase (JNK) pathways. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 32-78 30333878-7 2018 Metformin inhibited the Akt and extracellular signal-regulated kinase (ERK)1/2 pathways in A549 cells and activated the p38 MAPK and c-Jun N-terminal kinase (JNK) pathways. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 120-123 30333878-8 2018 Furthermore, in the presence of metformin, inhibitors of the p38 MAPK and JNK signaling pathway at different concentrations did not affect the levels of Nrf2, but inhibitors of the Akt and ERK1/2 pathway at different doses reduced the expression of Nrf2. Metformin 32-41 mitogen-activated protein kinase 1 Homo sapiens 61-64 29760016-7 2018 When applied to cultured cardiomyocytes, insulin and metformin increased titin phosphorylation at S4010, S4099, and S11878 via enhanced ERK1/2 (extracellular signal regulated kinase 1/2) and PKCalpha (protein kinase Calpha) activity; NRG-1 application enhanced ERK1/2 activity but reduced PKCalpha activity. Metformin 53-62 mitogen-activated protein kinase 1 Homo sapiens 144-185 30023463-7 2018 Our study shows that both of the two signaling pathways can be blocked by this combinational strategy: metformin suppressed both pathways by inhibiting the phosphorylation of ERK, 4E-BP1 and S6, and BEZ235 suppressed PI3K/AKT/ mTOR pathway by reducing the phosphorylation of 4E-BP1 and S6. Metformin 103-112 mitogen-activated protein kinase 1 Homo sapiens 175-178 28927780-7 2017 Metformin inhibited ERK1/2, JNK, and PI3K/Akt, but activated p38 pathway in these two cells. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 61-64 29467552-11 2018 The inhibitory effects of metformin on activated HSCs were mediated by inhibiting the Akt/mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) pathways via the activation of adenosine monophosphate-activated protein kinase (AMPK). Metformin 26-35 mitogen-activated protein kinase 1 Homo sapiens 131-168 29467552-11 2018 The inhibitory effects of metformin on activated HSCs were mediated by inhibiting the Akt/mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) pathways via the activation of adenosine monophosphate-activated protein kinase (AMPK). Metformin 26-35 mitogen-activated protein kinase 1 Homo sapiens 170-173 29285650-10 2018 Furthermore, gemigliptin augments the inhibitory effect of metformin on proliferation and migration through involvement of matrix metalloproteinase-2, matrix metalloproteinase-9, p53, p21, VCAM-1, and ERK in thyroid carcinoma cells. Metformin 59-68 mitogen-activated protein kinase 1 Homo sapiens 201-204 29351188-8 2018 Metformin promoted HUVEC migration and inhibited apoptosis via upregulation of vascular endothelial growth factor (VEGF) receptors (VEGFR1/R2), fatty acid binding protein 4 (FABP4), ERK/mitogen-activated protein kinase signaling, chemokine ligand 8, lymphocyte antigen 96, Rho kinase 1 (ROCK1), matrix metalloproteinase 16 (MMP16) and tissue factor inhibitor-2 under hyperglycemia-chemical hypoxia. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 182-185 28927780-9 2017 The combination of specific inhibitors of ERK1/2, JNK or PI3K/Akt pathway and metformin further promoted cell apoptosis and the up-regulation of p21, Bax, Bad, cleaved caspase-3 and -9 as well as the down-regulation of Bcl-2 mediated by metformin alone, but inhibition of p38 pathway exhibited the opposite results. Metformin 78-87 mitogen-activated protein kinase 1 Homo sapiens 272-275 28335557-0 2017 ROS Production and ERK Activity Are Involved in the Effects of d-beta-Hydroxybutyrate and Metformin in a Glucose Deficient Condition. Metformin 90-99 mitogen-activated protein kinase 1 Homo sapiens 19-22 28335557-11 2017 We demonstrate that glucose deficiency-induced cytotoxicity is mediated by ERK inhibition through ROS production, which is attenuated by D-BHB and intensified by metformin. Metformin 162-171 mitogen-activated protein kinase 1 Homo sapiens 75-78 27424158-9 2016 Experiments on MAPKs showed effective inhibitory potential of exenatide toward p38, JNK, and ERK, whereas metformin inhibited JNK and ERK only. Metformin 106-115 mitogen-activated protein kinase 1 Homo sapiens 134-137 28230206-7 2017 Overexpression of miR-21 abrogated the metformin-mediated inhibition of endothelial cells proliferation, migration, tubule formation and the TGF-beta-induced AKT, SMAD- and ERK-dependent phosphorylations, and conversely, down-regulation of miR-21 aggravated metformin"s action and revealed significant promotion effects. Metformin 39-48 mitogen-activated protein kinase 1 Homo sapiens 173-176 27699813-9 2017 Inversely, inhibition of MEK or treatment with metformin activated FOXO3a through inactivation of ERK signaling and suppressed the viability of LNCaP and 22Rv1 cells in a dose-dependent manner. Metformin 47-56 mitogen-activated protein kinase 1 Homo sapiens 98-101 27424158-12 2016 In conclusion, here, we report that metformin and exenatide inhibit the proinflammatory phenotype of human monocytes/macrophages via influence on MAPK, C/EBP beta, and NFkappaB. Metformin 36-45 mitogen-activated protein kinase 1 Homo sapiens 146-150 26802022-8 2016 The results demonstrated that metformin activated AMPK and decreased phosphorylation of Akt and Erk. Metformin 30-39 mitogen-activated protein kinase 1 Homo sapiens 96-99 26802022-9 2016 Furthermore, combinations of metformin with either Akt or Erk inhibitors synergistically diminished cancer proliferation, suggesting the involvement of Akt- and Erk- related pathways. Metformin 29-38 mitogen-activated protein kinase 1 Homo sapiens 161-164 26695692-0 2016 Metformin Restrains Pancreatic Duodenal Homeobox-1 (PDX-1) Function by Inhibiting ERK Signaling in Pancreatic Ductal Adenocarcinoma. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 82-85 26695692-10 2016 Metformin inhibited EGF-stimulated PDX-1 expression with an accompanied inhibition of ERK kinase activation in PANC- 1 cells. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 86-89 26695692-11 2016 Taken together, our studies show that PDX-1 is a potential novel target for metformin in PDAC cells and that metformin may exert its anticancer action in PDAC by down-regulating PDX-1 via a mechanism involving inhibition of ERK signaling. Metformin 109-118 mitogen-activated protein kinase 1 Homo sapiens 224-227 26391180-0 2015 Metformin Increases Sensitivity of Pancreatic Cancer Cells to Gemcitabine by Reducing CD133+ Cell Populations and Suppressing ERK/P70S6K Signaling. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 126-129 26186064-3 2015 We have also shown that metformin activates the ERK pathway in Ph+ALL cells, SUP-B15, a side effect that can be overcome by U0126 (MEK1/2 inhibitor) or imatinib. Metformin 24-33 mitogen-activated protein kinase 1 Homo sapiens 48-51 25245054-0 2014 Metformin inhibits the invasion of human hepatocellular carcinoma cells and enhances the chemosensitivity to sorafenib through a downregulation of the ERK/JNK-mediated NF-kappaB-dependent pathway that reduces uPA and MMP-9 expression. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 151-154 25846811-9 2015 We found an inverse correlation between the intensity of ERK activity and the degree of AMPK activation after stimulation with either glucose deprivation or metformin. Metformin 157-166 mitogen-activated protein kinase 1 Homo sapiens 57-60 25846811-10 2015 We also found that the inhibition of ERK activity by U0126 restored AMPK activation after metformin treatment. Metformin 90-99 mitogen-activated protein kinase 1 Homo sapiens 37-40 25846811-12 2015 Importantly, metformin induced ERK activation by suppressing the protein levels of dual specificity phosphatase 6, a negative regulator of ERK. Metformin 13-22 mitogen-activated protein kinase 1 Homo sapiens 31-34 25846811-12 2015 Importantly, metformin induced ERK activation by suppressing the protein levels of dual specificity phosphatase 6, a negative regulator of ERK. Metformin 13-22 mitogen-activated protein kinase 1 Homo sapiens 139-142 25846811-13 2015 This crosstalk between AMPK and ERK could diminish the antileukemic activity of metformin. Metformin 80-89 mitogen-activated protein kinase 1 Homo sapiens 32-35 26052399-6 2015 Metformin (through 5"-adenosine monophosphate-activated protein kinase pathway activation) and statins (through 3-hydroxy-3-methylglutaryl coenzyme A inhibition) show anti-tumoral properties modifying several steps of RAS/RAF/MEK/ERK, PI3K/AKT/mTOR and Wnt/beta-catenin signaling cascades. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 230-233 25493642-0 2014 Dose-Dependent AMPK-Dependent and Independent Mechanisms of Berberine and Metformin Inhibition of mTORC1, ERK, DNA Synthesis and Proliferation in Pancreatic Cancer Cells. Metformin 74-83 mitogen-activated protein kinase 1 Homo sapiens 106-109 25245054-9 2014 In conclusion, metformin inhibits the migration and invasion of HCC cells by suppressing the ERK/JNK-mediated NF-kappaB-dependent pathway, and thereby reducing uPA and MMP-9 expression. Metformin 15-24 mitogen-activated protein kinase 1 Homo sapiens 93-96 24480115-1 2014 OBJECTIVE: To assess the effect of metformin on expression of Akt, ERK, PI3K and GLUT4, proteins associated with the growth factor signaling cascade, in human endometrial stromal cells after stimulation with androgen and insulin. Metformin 35-44 mitogen-activated protein kinase 1 Homo sapiens 67-70 24788596-5 2014 Furthermore, metformin sensitized ICC cells to certain chemotherapeutic agents, such as sorafenib, 5-fluorouracil and As2O3 by targeting the AMPK/mTOR/HIF-1alpha/MRP1 pathway and ERK. Metformin 13-22 mitogen-activated protein kinase 1 Homo sapiens 179-182 24446492-4 2014 For instance, the derivatives of cannabis and an anti-diabetic agent, metformin, both are able to inhibit ERK, which is commonly activated in TC cells. Metformin 70-79 mitogen-activated protein kinase 1 Homo sapiens 106-109 23707609-0 2013 Metformin inhibits heme oxygenase-1 expression in cancer cells through inactivation of Raf-ERK-Nrf2 signaling and AMPK-independent pathways. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 91-94 23707609-7 2013 We also found that metformin regulation of Nrf2 expression is mediated by a Keap1-independent mechanism and that metformin significantly attenuated Raf-ERK signaling to suppress Nrf2 expression in cancer cells. Metformin 113-122 mitogen-activated protein kinase 1 Homo sapiens 152-155 23707609-10 2013 These results highlight the Raf-ERK-Nrf2 axis as a new molecular target in anticancer therapy in response to metformin treatment. Metformin 109-118 mitogen-activated protein kinase 1 Homo sapiens 32-35 23257425-7 2012 MEK/ERK signaling pathway may be one of the molecular mechanisms of metformin on NB4 cells. Metformin 68-77 mitogen-activated protein kinase 1 Homo sapiens 4-7 23607966-5 2013 The clinically available adenosine monophosphate-activated protein kinase activator, metformin, which is an antidiabetic drug, prevents rapamycin-induced ERK activation and the development of mechanical hypersensitivity and spontaneous pain. Metformin 85-94 mitogen-activated protein kinase 1 Homo sapiens 154-157 23462329-7 2013 Metformin administration also caused a significant reduction in the phosphorylation of ribosomal S6 protein and ERK in these xenografts. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 112-115 23879009-13 2013 Metformin has antiproliferative properties; reduces the VEGF levels, causing a reduction in tumor vasculature; causes an increase in progesterone receptor, which increases the response to hormonal therapy; inhibits the expression of glyoxalase I, mediating resistance to chemotherapy; decreases in the concentration of human telomerase; reduces the activity of Akt and Erk kinases, key regulators of metabolism and progression of tumors and also inhibits the formation of metastases. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 369-372 21619869-9 2011 Metformin activated phosphorylation of p38 mitogen-activated protein kinase (MAPK); compound C inhibited metformin-activated phosphorylation of p38 MAPK. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 39-42 22575507-0 2012 Metformin induces differentiation in acute promyelocytic leukemia by activating the MEK/ERK signaling pathway. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 88-91 22575507-4 2012 Further analysis revealed that a strong synergistic effect existed between metformin and all-trans retinoic acid (ATRA) during APL cell maturation and that metformin induced the hyperphosphorylation of extracellular signal-regulated kinase (ERK) in APL cells. Metformin 156-165 mitogen-activated protein kinase 1 Homo sapiens 202-239 22575507-4 2012 Further analysis revealed that a strong synergistic effect existed between metformin and all-trans retinoic acid (ATRA) during APL cell maturation and that metformin induced the hyperphosphorylation of extracellular signal-regulated kinase (ERK) in APL cells. Metformin 156-165 mitogen-activated protein kinase 1 Homo sapiens 241-244 22575507-5 2012 U0126, a specific MEK/ERK activation inhibitor, abrogated metformin-induced differentiation. Metformin 58-67 mitogen-activated protein kinase 1 Homo sapiens 22-25 21995500-0 2012 Inhibition of p42 MAPK using a nonviral vector-delivered siRNA potentiates the anti-tumor effect of metformin in prostate cancer cells. Metformin 100-109 mitogen-activated protein kinase 1 Homo sapiens 14-22 21995500-1 2012 AIMS: The aim of this work was to study if a G1-polyamidoamine dendrimer/siRNA dendriplex can remove the p42 MAPK protein in prostate cancer cells and to potentiate the anti-tumoral effect of the antidiabetic drug metformin and taxane docetaxel. Metformin 214-223 mitogen-activated protein kinase 1 Homo sapiens 105-113 21995500-5 2012 RESULTS: The dendriplex siRNA/G1-polyamidoamine dendrimer decreased both p42 MAPK mRNA and protein levels by more than 80%, which potentiates the anti-tumoral effects of metformin. Metformin 170-179 mitogen-activated protein kinase 1 Homo sapiens 73-81 21619869-10 2011 SB203580, as an inhibitor of p38 MAPK, significantly inhibited metformin-induced MUC5B mRNA expression, while U0126, as an inhibitor of ERK1/2 MAPK, had no effect. Metformin 63-72 mitogen-activated protein kinase 1 Homo sapiens 29-32 21619869-11 2011 In addition, knockdown of p38 MAPK by p38 MAPK siRNA significantly blocked metformin-induced MUC5B mRNA expression. Metformin 75-84 mitogen-activated protein kinase 1 Homo sapiens 26-29 21619869-11 2011 In addition, knockdown of p38 MAPK by p38 MAPK siRNA significantly blocked metformin-induced MUC5B mRNA expression. Metformin 75-84 mitogen-activated protein kinase 1 Homo sapiens 38-41 21776823-0 2011 Antidiabetic drug metformin induces apoptosis in human MCF breast cancer via targeting ERK signaling. Metformin 18-27 mitogen-activated protein kinase 1 Homo sapiens 87-90 21776823-10 2011 Finally, SAPK/JNK, known to be involved in apoptosis, was activated in cells treated with metformin and the activation appeared to occur downstream of ERK. Metformin 90-99 mitogen-activated protein kinase 1 Homo sapiens 151-154 21776823-11 2011 All these results suggested that metformin activated p53, Bax, and induced tumor cell apoptosis through the ERK signaling pathway. Metformin 33-42 mitogen-activated protein kinase 1 Homo sapiens 108-111 19574398-9 2009 Involvement of the ERK signaling pathway was demonstrated by the significant increase in phosphorylated ERK-1,2 with the combined metformin and insulin treatment. Metformin 130-139 mitogen-activated protein kinase 1 Homo sapiens 19-22 20590612-0 2010 Metformin blocks migration and invasion of tumour cells by inhibition of matrix metalloproteinase-9 activation through a calcium and protein kinase Calpha-dependent pathway: phorbol-12-myristate-13-acetate-induced/extracellular signal-regulated kinase/activator protein-1. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 214-251 20590612-7 2010 In addition, metformin strongly repressed the PMA-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and protein kinase C(PKC)alpha, whereas the phosphorylation of p38 mitogen-activated protein kinase was not affected by metformin. Metformin 13-22 mitogen-activated protein kinase 1 Homo sapiens 77-114 20590612-7 2010 In addition, metformin strongly repressed the PMA-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and protein kinase C(PKC)alpha, whereas the phosphorylation of p38 mitogen-activated protein kinase was not affected by metformin. Metformin 13-22 mitogen-activated protein kinase 1 Homo sapiens 116-119 20590612-10 2010 CONCLUSIONS AND IMPLICATIONS: Metformin inhibited PMA-induced invasion and migration of human fibrosarcoma cells via Ca(2+)-dependent PKCalpha/ERK and JNK/AP-1-signalling pathways. Metformin 30-39 mitogen-activated protein kinase 1 Homo sapiens 143-146 16385087-6 2006 Furthermore, metformin suppressed IL-1beta-induced activation of the pro-inflammatory phosphokinases Akt, p38, and Erk, but did not affect PI3 kinase (PI3K) activity. Metformin 13-22 mitogen-activated protein kinase 1 Homo sapiens 115-118 34944598-0 2021 Metformin Improves Stemness of Human Adipose-Derived Stem Cells by Downmodulation of Mechanistic Target of Rapamycin (mTOR) and Extracellular Signal-Regulated Kinase (ERK) Signaling. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 128-165 34944598-0 2021 Metformin Improves Stemness of Human Adipose-Derived Stem Cells by Downmodulation of Mechanistic Target of Rapamycin (mTOR) and Extracellular Signal-Regulated Kinase (ERK) Signaling. Metformin 0-9 mitogen-activated protein kinase 1 Homo sapiens 167-170 34944598-8 2021 Investigating the possible underlying mechanism, we observed a decrease in the mTOR and ERK activity in metformin-treated ASCs. Metformin 104-113 mitogen-activated protein kinase 1 Homo sapiens 88-91 34944598-10 2021 We conclude that metformin treatment improves ASCs stemness by reducing mTOR and ERK signaling and enhancing autophagy. Metformin 17-26 mitogen-activated protein kinase 1 Homo sapiens 81-84 34716862-8 2021 Downregulation of ERK signaling, upregulation of AMPK pathway and precision in epithelial-mesenchymal transition (EMT) pathway which were assessed by RT-PCR and Western blot provide the evidence that the combination of drugs involved in the precision of altered molecular signaling Further our results suggest that Metformin act as a demethylating agent in anaplastic thyroid cancer cells by inducing the expression of NIS and TSHR. Metformin 315-324 mitogen-activated protein kinase 1 Homo sapiens 18-21 34078517-3 2021 High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation. Metformin 22-31 mitogen-activated protein kinase 1 Homo sapiens 421-424 34078517-3 2021 High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation. Metformin 217-226 mitogen-activated protein kinase 1 Homo sapiens 421-424 34078517-3 2021 High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation. Metformin 318-327 mitogen-activated protein kinase 1 Homo sapiens 421-424 34078517-4 2021 These results suggest that a low concentration of metformin inhibits osteoclast differentiation through PI3K/Akt and MAPK/ERK signaling pathway; high concentrations of metformin promote osteoclast apoptosis through PI3K/Akt and ERK signaling pathway. Metformin 50-59 mitogen-activated protein kinase 1 Homo sapiens 122-125 34078517-4 2021 These results suggest that a low concentration of metformin inhibits osteoclast differentiation through PI3K/Akt and MAPK/ERK signaling pathway; high concentrations of metformin promote osteoclast apoptosis through PI3K/Akt and ERK signaling pathway. Metformin 50-59 mitogen-activated protein kinase 1 Homo sapiens 228-231 34078517-4 2021 These results suggest that a low concentration of metformin inhibits osteoclast differentiation through PI3K/Akt and MAPK/ERK signaling pathway; high concentrations of metformin promote osteoclast apoptosis through PI3K/Akt and ERK signaling pathway. Metformin 168-177 mitogen-activated protein kinase 1 Homo sapiens 228-231