2012
DOI: 10.4161/cc.11.2.18813
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Metformin targets Stat3 to inhibit cell growth and induce apoptosis in triple-negative breast cancers

Abstract: A distinct group of breast cancers, called "basal" or "triple-negative" (TN) cancers express both basal cytokeratins and the epidermal growth factor receptor, but fail to express estrogen receptors, progesterone receptors or HER2 and have stem-like or mesenchymal features. They are particularly aggressive, are frequently chemo-resistant, with p53 mutation, up-regulation of IL-6 and Stat3. Because TN cells are particularly sensitive to the anti-diabetic agent metformin, we hypothesized that it may target JAK2/S… Show more

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Cited by 187 publications
(169 citation statements)
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“…Metformin is known to affect AMPK-mTOR-mediated signaling and to suppress STAT3 activity in vitro (27). In this study, we found that splenic CD19 + B cells from metformintreated Roquin san/san mice exhibited a significant increase in the expression of p-AMPK but a significant decrease in the expression of mTOR and STAT3 phosphorylation at tyrosine 705 (pSTAT3 Y705) and STAT3 phosphorylation at serine 727 (pSTAT3 S727) compared with vehicle-treated mice (Fig.…”
Section: Metformin Activates Ampk and Decreases Mtor And Stat3 Phosphsupporting
confidence: 48%
“…Metformin is known to affect AMPK-mTOR-mediated signaling and to suppress STAT3 activity in vitro (27). In this study, we found that splenic CD19 + B cells from metformintreated Roquin san/san mice exhibited a significant increase in the expression of p-AMPK but a significant decrease in the expression of mTOR and STAT3 phosphorylation at tyrosine 705 (pSTAT3 Y705) and STAT3 phosphorylation at serine 727 (pSTAT3 S727) compared with vehicle-treated mice (Fig.…”
Section: Metformin Activates Ampk and Decreases Mtor And Stat3 Phosphsupporting
confidence: 48%
“…Metformin has been reported to inhibit IkB kinase phosphorylation, IkBa degradation, and IL-6 production through AMPK activation (72)(73)(74). A previous study suggested that metformin inhibited STAT3 phosphorylation and downstream signaling in triple-negative breast cancer cells, suggesting that STAT3 is a critical regulator of metformin action (75). Recently, metformin has also been shown to increase the sensitivity of resistant cells to cisplatin by suppressing STAT3 activity without activation of AMPKa (76).…”
Section: Nfkb/stat3 Signaling Pathwaymentioning
confidence: 99%
“…The effect of metformin on triplenegative cell lines may, in part, be attributable to STAT3 inhibition (52).…”
Section: Metforminmentioning
confidence: 99%