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01-04-2013 | Viewpoint

Metformin: a case of divide and conquer

Author: Dimitrios Anastasiou

Published in: Breast Cancer Research | Issue 2/2013

Abstract

Metformin is a widely prescribed anti-diabetic drug and its use is associated with lower cancer incidence. The mechanisms by which metformin attenuates tumorigenesis are not clearly understood. In a paper published in Proceedings of the National Academy of Sciences of the United States of America, Hirsch and colleagues show that metformin interferes with a signaling pathway, mediated by the transcription factor NF-κB, which drives cell transformation and is required for the maintenance of cancer stem cells.

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Marusyk A, Almendro V, Polyak K: Intra-tumour heterogeneity: a looking glass for cancer?. Nat Rev Cancer. 2012, 12: 323-334.CrossRefPubMed

Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF: Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 2003, 100: 3983-3988. 10.1073/pnas.0530291100.CrossRefPubMedPubMedCentral

Dean M, Fojo T, Bates S: Tumour stem cells and drug resistance. Nat Rev Cancer. 2005, 5: 275-284. 10.1038/nrc1590.CrossRefPubMed

Iliopoulos D, Hirsch HA, Struhl K: An epigenetic switch involving NF-κB, Lin28, Let-7 microRNA, and IL6 links inflammation to cell transformation. Cell. 2009, 139: 693-706. 10.1016/j.cell.2009.10.014.CrossRefPubMedPubMedCentral

Iliopoulos D, Jaeger SA, Hirsch HA, Bulyk ML, Struhl K: STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer. Mol Cell. 2010, 39: 493-506. 10.1016/j.molcel.2010.07.023.CrossRefPubMedPubMedCentral

Pollak MN: Investigating metformin for cancer prevention and treatment: the end of the beginning. Cancer Discov. 2012, 2: 778-790. 10.1158/2159-8290.CD-12-0263.CrossRefPubMed

Hirsch HA, Iliopoulos D, Tsichlis PN, Struhl K: Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res. 2009, 69: 7507-7511. 10.1158/0008-5472.CAN-09-2994.CrossRefPubMedPubMedCentral

Iliopoulos D, Hirsch HA, Struhl K: Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types. Cancer Res. 2011, 71: 3196-3201. 10.1158/0008-5472.CAN-10-3471.CrossRefPubMedPubMedCentral

Hirsch HA, Iliopoulos D, Struhl K: Metformin inhibits the inflammatory response associated with cellular transformation and cancer stem cell growth. Proc Natl Acad Sci USA. 2013, 110: 972-977. 10.1073/pnas.1221055110.CrossRefPubMed

10.

DiDonato JA, Mercurio F, Karin M: NF-κB and the link between inflammation and cancer. Immunol Rev. 2012, 246: 379-400. 10.1111/j.1600-065X.2012.01099.x.CrossRefPubMed

11.

Iliopoulos D, Hirsch HA, Wang G, Struhl K: Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion. Proc Natl Acad Sci USA. 2011, 108: 1397-1402. 10.1073/pnas.1018898108.CrossRefPubMedPubMedCentral

12.

Gupta PB, Fillmore CM, Jiang G, Shapira SD, Tao K, Kuperwasser C, Lander ES: Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells. Cell. 2011, 146: 633-644. 10.1016/j.cell.2011.07.026.CrossRefPubMed

13.

Hardie DG, Ross FA, Hawley SA: AMP-activated protein kinase: a target for drugs both ancient and modern. Chem Biol. 2012, 19: 1222-1236. 10.1016/j.chembiol.2012.08.019.CrossRefPubMed

14.

Javeshghani S, Zakikhani M, Austin S, Bazile M, Blouin MJ, Topisirovic I, St-Pierre J, Pollak MN: Carbon source and myc expression influence the antiproliferative actions of metformin. Cancer Res. 2012, 72: 6257-6267. 10.1158/0008-5472.CAN-12-2907.CrossRefPubMed

15.

Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, Lander ES: Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009, 138: 645-659. 10.1016/j.cell.2009.06.034.CrossRefPubMedPubMedCentral

Title: Metformin: a case of divide and conquer
Author: Dimitrios Anastasiou
Publication date: 01-04-2013
Publisher: BioMed Central
Published in: Breast Cancer Research / Issue 2/2013
Electronic ISSN: 1465-542X
DOI: https://doi.org/10.1186/bcr3387

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