Metformin-Induced Killing of Triple-Negative Breast Cancer Cells Is Mediated by Reduction in Fatty Acid Synthase via miRNA-193b

Warburg O (1956) On respiratory impairment in cancer cells. Science 124(3215):269–270 Hilvo M et al (2011) Novel theranostic opportunities offered by characterization of altered membrane lipid metabolism in breast cancer progression. Cancer Res 71(9):3236–3245 Medes G, Thomas A, Weinhouse S (1953) Metabolism of neoplastic tissue. IV. A study of lipid synthesis in neoplastic tissue slices in vitro. Cancer Res 13(1):27–29 Ookhtens M et al (1984) Liver and adipose tissue contributions to newly formed fatty acids in an ascites tumor. Am J Physiol 247(1 Pt 2):R146–R153 Sabine JR, Abraham S, Chaikoff IL (1967) Control of lipid metabolism in hepatomas: insensitivity of rate of fatty acid and cholesterol synthesis by mouse hepatoma BW7756 to fasting and to feedback control. Cancer Res 27(4):793–799 Menendez JA, Lupu R (2007) Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer 7(10):763–777 Chajes V et al (2006) Acetyl-CoA carboxylase alpha is essential to breast cancer cell survival. Cancer Res 66(10):5287–5294 Alo PL et al (1996) Expression of fatty acid synthase (FAS) as a predictor of recurrence in stage I breast carcinoma patients. Cancer 77(3):474–482 Menendez JA, Lupu R (2006) Oncogenic properties of the endogenous fatty acid metabolism: molecular pathology of fatty acid synthase in cancer cells. Curr Opin Clin Nutr Metab Care 9(4):346–357 Menendez JA, Lupu R, Colomer R (2004) Inhibition of tumor-associated fatty acid synthase hyperactivity induces synergistic chemosensitization of HER-2/neu-overexpressing human breast cancer cells to docetaxel (taxotere). Breast Cancer Res Treat 84(2):183–195 Swinnen JV, Brusselmans K, Verhoeven G (2006) Increased lipogenesis in cancer cells: new players, novel targets. Curr Opin Clin Nutr Metab Care 9(4):358–365 Turrado C et al (2012) New synthetic inhibitors of fatty acid synthase with anticancer activity. J Med Chem 55(11):5013–5023 Knowles LM et al (2008) Inhibition of fatty-acid synthase induces caspase-8-mediated tumor cell apoptosis by up-regulating DDIT4. J Biol Chem 283(46):31378–31384 Pizer ES et al (1996) Fatty acid synthase (FAS): a target for cytotoxic antimetabolites in HL60 promyelocytic leukemia cells. Cancer Res 56(4):745–751 Samudio I et al (2010) Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction. J Clin Invest 120(1):142–156 Chuang HY, Chang YF, Hwang JJ (2011) Antitumor effect of orlistat, a fatty acid synthase inhibitor, is via activation of caspase-3 on human colorectal carcinoma-bearing animal. Biomed Pharmacother 65(4):286–292 Kridel SJ et al (2004) Orlistat is a novel inhibitor of fatty acid synthase with antitumor activity. Cancer Res 64(6):2070–2075 Deepa PR et al (2012) Therapeutic and toxicologic evaluation of anti-lipogenic agents in cancer cells compared with non-neoplastic cells. Basic Clin Pharmacol Toxicol 110(6):494–503 McGowan MM et al (2013) A proof of principle clinical trial to determine whether conjugated linoleic acid modulates the lipogenic pathway in human breast cancer tissue. Breast Cancer Res Treat 138(1):175–183 Puig T et al (2011) A novel inhibitor of fatty acid synthase shows activity against HER2 + breast cancer xenografts and is active in anti-HER2 drug-resistant cell lines. Breast Cancer Res 13(6):R131 Puig T et al (2009) Novel inhibitors of fatty acid synthase with anticancer activity. Clin Cancer Res 15(24):7608–7615 Romero IL et al (2012) Relationship of type II diabetes and metformin use to ovarian cancer progression, survival, and chemosensitivity. Obstet Gynecol 119(1):61–67 Gandini S et al (2013) Metformin and breast cancer risk. J Clin Oncol 31(7):973–974 Dowling RJ et al (2012) Metformin in cancer: translational challenges. J Mol Endocrinol 48(3):R31–R43 Goodwin PJ, Ligibel JA, Stambolic V (2009) Metformin in breast cancer: time for action. J Clin Oncol 27(20):3271–3273 Niraula S et al (2012) Metformin in early breast cancer: a prospective window of opportunity neoadjuvant study. Breast Cancer Res Treat 135(3):821–830 Algire C et al (2010) Metformin blocks the stimulative effect of a high-energy diet on colon carcinoma growth in vivo and is associated with reduced expression of fatty acid synthase. Endocr Relat Cancer 17(2):351–360 Vazquez Martin A et al (2013) The mitochondrial H(+)-ATP synthase and the lipogenic switch: new core components of metabolic reprogramming in induced pluripotent stem (iPS) cells. Cell Cycle 12(2):207–218 Vazquez‐Martin A et al (2012) Metformin limits the tumourigenicity of iPS cells without affecting their pluripotency. Sci Rep 2:964 Alimova IN et al (2009) Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro. Cell Cycle 8((6):909–915 Giles ED et al (2012) Obesity and overfeeding affecting both tumor and systemic metabolism activates the progesterone receptor to contribute to postmenopausal breast cancer. Cancer Res 72(24):6490–6501 Liu B et al (2009) Metformin induces unique biological and molecular responses in triple negative breast cancer cells. Cell Cycle 8(13):2031–2040 Wahdan‐Alaswad R et al (2013) Glucose promotes breast cancer aggression and reduces metformin efficacy. Cell Cycle 12(24):3759–3769 Deng XS et al (2012) Metformin targets Stat3 to inhibit cell growth and induce apoptosis in triple-negative breast cancers. Cell Cycle 11(2):367–376 Hirsch HA et al (2009) Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res 69(19):7507–7511 Zakikhani M et al (2006) Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res 66(21):10269–10273 Creighton CJ et al (2009) Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc Natl Acad Sci U S A 106(33):13820–13825 Honeth G et al (2008) The CD44+/CD24− phenotype is enriched in basal-like breast tumors. Breast Cancer Res 10(3):R53 Siddiqui RA et al (2005) Anticancer properties of propofol-docosahexaenoate and propofol-eicosapentaenoate on breast cancer cells. Breast Cancer Res 7(5):R645–R654 Sanlioglu AD et al (2005) Surface TRAIL decoy receptor-4 expression is correlated with trail resistance in MCF7 breast cancer cells. BMC Cancer 5:54 Dontu G et al (2003) In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev 17(10):1253–1270 Ginestier C et al (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1(5):555–567 Zhuang Y, Miskimins WK (2008) Cell cycle arrest in metformin treated breast cancer cells involves activation of AMPK, downregulation of cyclin D1, and requires p27Kip1 or p21Cip1. J Mol Signal 3:18 Cochrane DR et al (2010) MicroRNAs link estrogen receptor alpha status and dicer levels in breast cancer. Horm Cancer 1(6):306–319 Pandey PR et al (2011) Resveratrol suppresses growth of cancer stem-like cells by inhibiting fatty acid synthase. Breast Cancer Res Treat 130(2):387–398 Funabashi H et al (1989) Binding site of cerulenin in fatty acid synthetase. J Biochem 105(5):751–755 Pizer ES et al (1996) Inhibition of fatty acid synthesis induces programmed cell death in human breast cancer cells. Cancer Res 56(12):2745–2747 Chlebowski RT (2012) Obesity and breast cancer outcome: adding to the evidence. J Clin Oncol 30(2):126–128 Chlebowski RT et al (2012) Diabetes, metformin, and breast cancer in postmenopausal women. J Clin Oncol 30(23):2844–2852 Knowler WC et al (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346(6):393–403 Jiralerspong S et al (2009) Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol 27(20):3297–3302 Knobloch M et al (2013) Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis. Nature 493(7431):226–230 Wang X et al (2013) PPARgamma maintains ERBB2-positive breast cancer stem cells. Oncogene 32(49):5512–5521 Milgraum LZ et al (1997) Enzymes of the fatty acid synthesis pathway are highly expressed in situ breast carcinoma. Clin Cancer Res 3(11):2115–2120 Esslimani Sahla M et al (2007) Increased expression of fatty acid synthase and progesterone receptor in early steps of human mammary carcinogenesis. Int J Cancer 120(2):224–229 Chalbos D et al (1992) Progestin‐induced fatty acid synthetase in human mammary tumors: from molecular to clinical studies. J Steroid Biochem Mol Biol 43(1‐3):223–228 Joyeux C, Chalbos D, Rochefort H (1990) Effects of progestins and menstrual cycle on fatty acid synthetase and progesterone receptor in human mammary glands. J Clin Endocrinol Metab 70(5):1438–1444 Chalbos D et al (1990) Expression of the progestin‐induced fatty acid synthetase in benign mastopathies and breast cancer as measured by RNA in situ hybridization. J Natl Cancer Inst 82(7):602–606 Chalbos D et al (1990) Regulation of fatty acid synthetase by progesterone in normal and tumoral human mammary glands. Rev Esp Fisiol 46(1):43–46 Chambon M et al (1989) Progestins and androgens stimulate lipid accumulation in T47D breast cancer cells via their own receptors. J Steroid Biochem 33(5):915–922 Joyeux C, Rochefort H, Chalbos D (1989) Progestin increases gene transcription and messenger ribonucleic acid stability of fatty acid synthetase in breast cancer cells. Mol Endocrinol 3(4):681–686 Chalbos D et al (1987) Fatty acid synthetase and its mRNA are induced by progestins in breast cancer cells. J Biol Chem 262(21):9923–9926 Martel PM et al (2006) S14 protein in breast cancer cells: direct evidence of regulation by SREBP‐1c, superinduction with progestin, and effects on cell growth. Exp Cell Res 312(3):278–288 Menendez JA, Lupu R, Colomer R (2005) Obesity, fatty acid synthase, and cancer: serendipity or forgotten causal linkage? Mol Genet Metab 84(3):293–295 Menendez JA et al (2004) Novel signaling molecules implicated in tumor‐associated fatty acid synthase‐dependent breast cancer cell proliferation and survival: role of exogenous dietary fatty acids, p53‐p21WAF1/CIP1, ERK1/2 MAPK, p27KIP1, BRCA1, and NF‐kappaB. Int J Oncol 24(3):591–608 Seguin F et al (2012) The fatty acid synthase inhibitor orlistat reduces experimental metastases and angiogenesis in B16‐F10 melanomas. Br J Cancer 107(6):977–987 Zaytseva YY et al (2012) Inhibition of fatty acid synthase attenuates CD44‐associated signaling and reduces metastasis in colorectal cancer. Cancer Res 72(6):1504–1517 Fryer LG, Parbu‐Patel A, Carling D (2002) The Anti‐diabetic drugs rosiglitazone and metformin stimulate AMP‐activated protein kinase through distinct signaling pathways. J Biol Chem 277(28):25226–25232 Musi N et al (2002) Metformin increases AMP‐activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes 51(7):2074–2081 Zhou G et al (2001) Role of AMP‐activated protein kinase in mechanism of metformin action. J Clin Invest 108(8):1167–1174 Dowling RJ et al (2007) Metformin inhibits mammalian target of rapamycin‐dependent translation initiation in breast cancer cells. Cancer Res 67(22):10804–10812 Guo D et al (2009) The AMPK agonist AICAR inhibits the growth of EGFRvIII‐expressing glioblastomas by inhibiting lipogenesis. Proc Natl Acad Sci U S A 106(31):12932–12937 Zhao X et al (2012) Regulation of lipogenesis by cyclin‐dependent kinase 8‐mediated control of SREBP‐1. J Clin Invest 122(7):2417–2427 Lee KH et al (2011) Targeting energy metabolic and oncogenic signaling pathways in triple‐negative breast cancer by a novel adenosine monophosphate‐activated protein kinase (AMPK) activator. J Biol Chem 286(45):39247–39258 Bao B et al (2012) Metformin inhibits cell proliferation, migration and invasion by attenuating CSC function mediated by deregulating miRNAs in pancreatic cancer cells. Cancer Prev Res (Phila) 5(3):355–364 Blandino G et al (2012) Metformin elicits anticancer effects through the sequential modulation of DICER and c‐MYC. Nat Commun 3:865 Oliveras‐Ferraros C et al (2011) Micro(mi)RNA expression profile of breast cancer epithelial cells treated with the anti‐diabetic drug metformin: induction of the tumor suppressor miRNA let‐7a and suppression of the TGFbeta‐induced oncomiR miRNA‐181a. Cell Cycle 10(7):1144–1151 Loftus TM et al (2000) Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. Science 288(5475):2379–2381 Mao JH et al (2012) microRNA‐195 suppresses osteosarcoma cell invasion and migration in vitro by targeting FASN. Oncol Lett 4(5):1125–1129 Park JH et al (2011) Murine hepatic miRNAs expression and regulation of gene expression in diet‐induced obese mice. Mol Cells 31(1):33–38 Shirasaki T et al (2013) MicroRNA‐27a regulates lipid metabolism and inhibits hepatitis C virus replication in human hepatoma cells. J Virol 87(9):5270–5286 Zhong D et al (2013) MicroRNA‐613 represses lipogenesis in HepG2 cells by downregulating LXRalpha. Lipids Health Dis 12:32