The role of hypoxia-induced factor 1α in breast cancer

Abstract

Breast cancer usually grows very quickly, becoming insensitive to blood flow in nearby veins; because of that, inside solid tumors it’s possible to find a hypoxic environment, in other words, an environment where oxygen is less available. Another feature of cancer is its angiogenesis rate, because of the high energy demand, new blood vessels must be produced to take nutrients inside the solid tumor mass. Even with normal blood flow bringing the cancer oxygen and nutrients, its cells favor hypoxia, in an event known as Warburg Effect. According to the Warburg Effect, cells, even with normal oxygen rates, prefer to use fermentation instead of the citric acid cycle to produce ATP. For the cancer to operate normally in hypoxia, a transcription factor family is activated, known as hypoxia-induced factors (HIF), composed of a HIF-1β and a HIF-1α subunits. As HIF-1α is expressed during hypoxia, it is a great target for treatments and a breast cancer biomarker. Because of the role of HIF-1α in cancer and the high incidence of breast cancer worlwide, this review was performed in order to bring the most recent results concerning the role HIF-1α can exert in breast cancer development and progression.

Keywords

Breast neoplasms / hypoxia-induced factor 1 / HIF-1α

References

[1] World Health Organization. Cancer. Available from: http://www.who.int/news-room/fact-sheets/detail/cancer. [Last accessed on 21 May 2019]

[2] Courtnay R,Malik N,Tortorella SM.Cancer metabolism and the Warburg effect: the role of HIF-1 and PI3K..Mol Biol Rep2015;42:841-51

[3] McIntyre A,Ledaki I,Singleton D.Disrupting hypoxia-induced bicarbonate transport acidifies tumor cells and suppresses tumor growth..Cancer Res2016;76:3744-55

[4] Wilkins SE,Hancock RL.Targeting protein - protein interactions in the HIF system..Chem Med Chem2016;11:773-86 PMCID:PMC4848768

[5] Smith TG,Ratcliffe PJ.The human side of hypoxia-inducible factor..Br J of Haematology2008;141:325-34 PMCID:PMC2408651

[6] Xiang L,Hu H,Bullen JW.HIF-1α and TAZ serve as reciprocal co-activators in human breast cancer cells..Oncotarget2015;6:11768-78 PMCID:PMC4494903

[7] Xiang L,Hu H,Luo W.Hypoxia-inducible factor 1 mediates TAZ expression and nuclear localization to induce the breast cancer stem cell phenotype..Oncotarget2014;5:12509-27 PMCID:PMC4350363

[8] Soni S.HIF-1 in cancer therapy: two decade long story of a transcription factor..Acta Oncol2017;56:503-15

[9] Lai F,Liu X,Xie P.LXY6090 - a novel manassantin A derivative - limits breast cancer growth through hypoxia-inducible factor-1 inhibition..Onco Targets Ther2016;9:3829-40 PMCID:PMC4928675

[10] Sarkar R,Biswas J.Phenethyl isothiocyanate, by virtue of its antioxidant activity, inhibits invasiveness and metastatic potential of breast cancer cells: HIF-1α as a putative target..Free Radic Res2016;50:84-100

[11] Zhou Z,Zhang ZS,Zheng Y.Human rhomboid family-1 (RHBDF1) suppresses oxygen-independent degradation of hypoxia-inducible factor-1α in breast cancer..Cancer Res2014;74:2719-30

[12] Huang Z,Wei G,Zheng Y.RAS protein activator-like 1 is functionally involved in hypoxia resistance in breast cancer cells by targeting hypoxia inducible factor-1α..Oncol Lett2017;14:3839-45 PMCID:PMC5588051

[13] Nalwoga H,Arnes JB,Akslen LA.Strong expression of hypoxia-inducible factor-1α (HIF-1α) is associated with Axl expression and features of aggressive tumors in African breast cancer..PLoS One2016;11:e0146823 PMCID:PMC4711940

[14] Cai FF,Pan X,Lin XY.Prognostic value of plasma levels of HIF-1a and PGC-1a in breast cancer..Oncotarget2016;7:77793-806 PMCID:PMC5363621

[15] Li M,Zhang J,Yang Y.Expression of LPA2 is associated with poor prognosis in human breast cancer and regulates HIF-1α expression and breast cancer cell growth..Oncol Rep2016;6:3479-87

[16] Sun G,Hu W.Correlation between HIF-1α expression and breast cancer risk: a meta-analysis..Breast J2014;20:213-15

[17] Tanaka T,Nakazawa H,Oki M.Low-dose farnesyltransferase inhibitor suppresses HIF-1α and snail expression in triple-negative breast cancer MDA-MB-231 cells in vitro..J. Cell. Physiol2017;232:192-201

[18] Badowska-Kozakiewicz A,Patera J.Expression of Hypoxia-Inducible Factor 1α in Invasive Breast Cancer with Metastasis to Lymph Nodes: Correlation with Steroid Receptors, HER2 and EPO-R..Adv Clin Exp Med2016;25:741-50

[19] Villa JC,Brandes AH,Villa CH.Non-transcriptional role of Hif-1α in activation of γ-secretase and Notch signaling in breast cancer..Cell Rep2014;8:1077-92 PMCID:PMC4346175

[20] Lopez-Haber C,Casado-Medrano V.Heregulin/ErbB3 signaling enhances CXCR4-driven rac1 activation and breast cancer cell motility via hypoxia-inducible factor 1α..Mol and Cellular Bio2016;36:2011-26 PMCID:PMC4946436

[21] Huang R,Zong X,Ma L.Monomethyltransferase SETD8 regulates breast cancer metabolism via stabilizing hypoxia-inducible factor 1a..Cancer Lett2017;390:1-10

[22] Changchun K,Ke S,Lei W.Interleukin-17 augments tumor necrosis factor α-mediated increase of hypoxia-inducible factor-1α and inhibits vasodilator-stimulated phosphoprotein expression to reduce the adhesion of breast cancer cells..Oncol Lett2017;13:3253-60 PMCID:PMC5431294

[23] Dewangan J,Rath SK.Centchroman regulates breast cancer angiogenesis via inhibition of HIF-1α/VEGFR2 signalling axis..Life Sci2018;193:9-19

[24] Filippi I,Naldini A.Interleukin-1β Affects MDAMB231 Breast Cancer Cell Migration under Hypoxia: Role of HIF-1α and NFκB Transcription Factors..Mediators of Inflamm2015;2105:789414 PMCID:PMC4677223

[25] Dong M,Chen ZH,Li X.Aberrant expression of enhancer of zeste homologue 2, correlated with HIF-1α, refines relapse risk and predicts poor outcome for breast cancer..Oncol Rep2014;32:1101-7

[26] Rajkovic-Molek K,Hadžisejdić I.The prognostic importance of nuclear factor kB and hypoxia-inducible factor 1a in relation to the breast cancer subtype and the overall survival..Appl Immunohistochem Mol Morphol2014;22:464-70

[27] Yang J,Jones DT,Bridges E.Estrogen receptor-α directly regulates the hypoxia-inducible factor 1 pathway associated with antiestrogen response in breast cancer..PNAS2015;112:15172-77 PMCID:PMC4679044

[28] Jia X,Lei L,Li J.Basal and therapy-driven hypoxia-inducible factor-1α confers resistance to endocrine therapy in estrogen receptor-positive breast cancer..Oncotarget2015;6:8648-62 PMCID:PMC4496173

[29] Woo YM,Lee EJ,Jeong SH.Inhibition of aerobic glycolysis Represses Akt/mTOR/HIF-1α axis and restores tamoxifen sensitivity in antiestrogen-resistant breast cancer cells..PLoS One2015;10:e0132285 PMCID:PMC4497721

[30] Yehia L,Jabbour M,Fakhruddin N.Expression of HIF-1α and markers of angiogenesis are not significantly different in triple negative breast cancer compared to other breast cancer molecular subtypes: implications for future therapy..PLoS One2015;10:e0129356 PMCID:PMC4457831

[31] Kazi AA,Schech AJ,Sabnis G.Nonhypoxic regulation and role of hypoxia-inducible factor 1 in aromatase inhibitor resistant breast cancer..Breast Cancer Res2014;16:R15 PMCID:PMC3978891

[32] Li YP,Shi PC,Wu HM.4-Hydroxynonenal promotes growth and angiogenesis of breast cancer cells through HIF-1α stabilization..Asian Pac J Cancer Prev2014;15:10151-56

[33] Aghazadeh S.Activation of STAT3/HIF-1α/Hes-1 axis promotes Trastuzumab resistance in HER2-overexpressing breast cancer cells via down-regulation of PTEN..Biochim Biophys Acta Gen Subj2017;1861:1970-80

[34] Zhong R,Chen G,Gao Y.The role of hypoxia-inducible factor-1α in radiation-induced autophagic cell death in breast cancer cells..Tumour Biol2015;36:7077

[35] Li X,Liu A.Long non-coding RNA UCA1 enhances tamoxifen resistance in breast cancer cells through a miR-18a-HIF1α feedback regulatory loop..Tumour Biol2016;37:14733-43

[36] Li G,Liu L,Zhou J.Tanshinone IIA inhibits HIF-1α and VEGF expression in breast cancer cells via mTOR/p70S6K/RPS6/4E-BP1 signaling pathway..PLoS One2015;10:e0117440 PMCID:PMC4320086

[37] Cho KH,Cho DY,Lee HY.Breast cancer metastasis suppressor 1 (BRMS1) attenuates TGF-β1-induced breast cancer cell aggressiveness through downregulating HIF-1α expression..BMC Cancer2015;15:829 PMCID:PMC4628375

[38] Wang F,Shi Y,Zhao J.Down-regulation of hypoxia-inducible factor-1 suppresses malignant biological behavior of triple-negative breast cancer cells..Int J Clin Exp Med2014;7:3933-40 PMCID:PMC4276159

[39] Shao C,Fu J.The potential role of Brachyury in inducing epithelial-to-mesenchymal transition (EMT) and HIF-1a expression in breast cancer cells..Biochem Biophys Res Commun2015;467:1083-89

[40] Fu P,Chen W,Lv K.Tanshinone IIA blocks epithelial-mesenchymal transition through HIF-1α downregulation, reversing hypoxia-induced chemotherapy resistance in breast cancer cell lines..Oncol Rep2014;31:2561-68

[41] Li Z,Hu L,Wu Z.Anterior gradient 2 is a binding stabilizer of hypoxia inducible factor-1α that enhances CoCl2 -induced doxorubicin resistance in breast cancer cells..Cancer Sci2015;106:1041-49 PMCID:PMC4556394

[42] Xu S.Tanshinone II-A: new perspectives for old remedies..Expert Opin Ther Pat.2013;23:149-53

[43] von Wahlde MK,Ruckert C,Kiesel L.The anti-androgen drug dutasteride renders triple negative breast cancer cells more sensitive to chemotherapy via inhibition of HIF-1α-/VEGF-signaling..Gynecol Endocrinol2015;31:160-64

[44] Luo HQ,Zhong WT,Liu FM.EGCG decreases the expression of HIF-1α and VEGF and cell growth in MCF-7 breast cancer cells..J BUON2014;19:435-39

[45] Yang H,Zou Y,Jiang W.M410, a combretastatin A4 analogue, disrupts microtubules and inhibits HIF-1α in human breast cancer cells..Oncol Rep2015;34:334-40

[46] Ghattass K,Zibara K,Haddadin MJ.The quinoxaline di-N-oxide DCQ blocks breast cancer metastasis in vitro and in vivo by targeting the hypoxia inducible factor-1 pathway..Mol Cancer2014;13:12-24 PMCID:PMC3932516

[47] Liu Y,Sun X.EMMPRIN down-regulating miR-106a/b modifies breast cancer stem-like cell properties via interaction with fibroblasts through STAT3 and HIF-1α..Sci Rep2016;6:28329 PMCID:PMC4914854

[48] Pakravan K,Sadeghizadeh M,Mossahebi-Mohammadi M.MicroRNA-100 shuttled by mesenchymal stem cell-derived exosomes suppresses in vitro angiogenesis through modulating the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells..Cell Oncol2017;40:457-70

[49] Kuo CY,Hou P,Ma H.HIF-1-alpha links mitochondrial perturbation to the dynamic acquisition of breast cancer tumorigenicity..Oncotarget2016;7:34052-69 PMCID:PMC5085137

[50] Tosatto A,Kummerow C,Blacker TS.The mitochondrial calcium uniporter regulates breast cancer progression via HIF-1α..EMBO Mol Med2016;8:569-85 PMCID:PMC4864890

[51] Zhu X,Li S,Zou H.HIF-1α decoy oligodeoxynucleotides inhibit HIF-1α signaling and breast cancer proliferation..Int J Oncol2015;46:215-22

[52] Wei L,Qiao C,Li Z.Oroxylin A inhibits glycolysis-dependent proliferation of human breast cancer via promoting SIRT3-mediated SOD2 transcription and HIF1α destabilization..Cell Death Dis2015;6:e1714 PMCID:PMC4650553

[53] Jeong YJ,Magae J,Park KG.Ascofuranone suppresses EGF-induced HIF-1α protein synthesis by inhibition of the Akt/mTOR/ p70S6K pathway in MDA-MB-231 breast cancer cells..Toxicol. Appl. Pharmacol2013;273:542-50

[54] Qiu SP,Shi HL,Huang F.Notoginsenoside Ft1 down-regulates HIF-1α, inhibits cell proliferation, decreases migration and promotes apoptosis in breast cancer cells..Yao Xue Xue Bao2016;51:1091-97(in Chinese)

[55] Li J,Jiang H.Andrographolide inhibits hypoxia-inducible factor-1 through phosphatidylinositol 3-kinase/AKT pathway and suppresses breast cancer growth..Onco Targets Ther2015;8:427-35 PMCID:PMC4335622

[56] Esfandiary A,Abedin-Do A,Shirzad M.Lactobacilli modulate hypoxia-inducible factor (HIF)-1 regulatory pathway in triple negative breast cancer cell line..Cell J2016;18:237-44 PMCID:PMC4988423

[57] Wei Z,Tao L,Zhu Z.Diallyl trisulfides, a natural histone deacetylase inhibitor, attenuate HIF-1α synthesis, and decreases breast cancer metastasis..Mol Carcinog2017;56:2317-31

[58] Pan Y,Zhao Y,Zheng X.Berberine reverses hypoxia-induced chemoresistance in breast cancer through the inhibition of AMPK-HIF-1α..Int J Biol Sci2017;13:794-803 PMCID:PMC5485634