Reference Detail

Ref Type

Journal Article

PMID

(17062558)

Authors

Zakikhani M, Dowling R, Fantus IG, Sonenberg N, Pollak M

Title

Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Cancer research	66	21	2006 Nov 1	10269-73	Cancer Res

URL

Abstract Text

Recent population studies provide clues that the use of metformin may be associated with reduced incidence and improved prognosis of certain cancers. This drug is widely used in the treatment of type 2 diabetes, where it is often referred to as an "insulin sensitizer" because it not only lowers blood glucose but also reduces the hyperinsulinemia associated with insulin resistance. As insulin and insulin-like growth factors stimulate proliferation of many normal and transformed cell types, agents that facilitate signaling through these receptors would be expected to enhance proliferation. We show here that metformin acts as a growth inhibitor rather than an insulin sensitizer for epithelial cells. Breast cancer cells can be protected against metformin-induced growth inhibition by small interfering RNA against AMP kinase. This shows that AMP kinase pathway activation by metformin, recently shown to be necessary for metformin inhibition of gluconeogenesis in hepatocytes, is also involved in metformin-induced growth inhibition of epithelial cells. The growth inhibition was associated with decreased mammalian target of rapamycin and S6 kinase activation and a general decrease in mRNA translation. These results provide evidence for a mechanism that may contribute to the antineoplastic effects of metformin suggested by recent population studies and justify further work to explore potential roles for activators of AMP kinase in cancer prevention and treatment.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
STK11 loss	Advanced Solid Tumor	no benefit	Metformin	Preclinical - Cell culture	Actionable	In a preclinical study, Glucophage (metformin) was unable to inhibit cancer cell growth in cancer cell lines with biallelic loss of STK11 (PMID: 17062558, PMID: 18006825).	18006825 17062558
STK11 wild-type	Advanced Solid Tumor	sensitive	Metformin	Preclinical - Cell culture	Actionable	In a preclinical studies, Glucophage (metformin) inhibited cancer cell growth by activating the AMP kinase pathway in a variety of cancer cell lines that retained one functional allele of STK11 (PMID: 17062558, PMID: 18006825).	18006825 17062558