Oncogenic metabolic reprogramming in breast cancer: focus on signaling pathways and mitochondrial genes.
BC
Metabolic reprogramming
Mitochondria
Signaling
Journal
Medical oncology (Northwood, London, England)
ISSN: 1559-131X
Titre abrégé: Med Oncol
Pays: United States
ID NLM: 9435512
Informations de publication
Date de publication:
11 May 2023
11 May 2023
Historique:
received:
01
02
2023
accepted:
20
04
2023
medline:
15
5
2023
pubmed:
12
5
2023
entrez:
11
5
2023
Statut:
epublish
Résumé
Oncogenic metabolic reprogramming impacts the abundance of key metabolites that regulate signaling and epigenetics. Metabolic vulnerability in the cancer cell is evident from the Warburg effect. The research on metabolism in the progression and survival of breast cancer (BC) is under focus. Oncogenic signal activation and loss of tumor suppressor are important regulators of tumor cell metabolism. Several intrinsic and extrinsic factors contribute to metabolic reprogramming. The molecular mechanisms underpinning metabolic reprogramming in BC are extensive and only partially defined. Various signaling pathways involved in the metabolism play a significant role in the modulation of BC. Notably, PI3K/AKT/mTOR pathway, lactate-ERK/STAT3 signaling, loss of the tumor suppressor Ras, Myc, oxidative stress, activation of the cellular hypoxic response and acidosis contribute to different metabolic reprogramming phenotypes linked to enhanced glycolysis. The alterations in mitochondrial genes have also been elaborated upon along with their functional implications. The outcome of these active research areas might contribute to the development of novel therapeutic interventions and the remodeling of known drugs.
Identifiants
pubmed: 37170010
doi: 10.1007/s12032-023-02037-2
pii: 10.1007/s12032-023-02037-2
doi:
Substances chimiques
Phosphatidylinositol 3-Kinases
EC 2.7.1.-
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
174Subventions
Organisme : University Grants Commission, India
ID : KL1216200313
Organisme : Council for Scientific and Industrial Research India
ID : 09/1051(0038)/2019-EMR-1
Organisme : Council for Scientific and Industrial Research, India
ID : 09/1051(0042)/2019-EMR-1
Organisme : Science and Engineering Research Board
ID : SRG/2021/001806
Informations de copyright
© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
Références
Momenimovahed Z, Salehiniya H. Epidemiological characteristics of and risk factors for breast cancer in the world. Breast Cancer: Targets and Therapy. 2019;11:151.
pubmed: 31040712
Sung, H., J. Ferlay, R.L. Siegel, M. Laversanne, I. Soerjomataram, A. Jemal, et al., Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 2021. 71(3): p. 209–249.
Siegel R, Bandi P, Jemal A. Breast cancer statistics, 2011. CA Cancer J Clin. 2011;61:409–18.
pubmed: 21969133
Sung H, Ferlay J, Siegel RL. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.
pubmed: 33538338
doi: 10.3322/caac.21660
Łukasiewicz S, Czeczelewski M, Forma A. Breast cancer-epidemiology, risk factors, classification, prognostic markers, and current treatment strategies-an updated review. Cancers. 2021;13(17):4287.
pubmed: 34503097
pmcid: 8428369
doi: 10.3390/cancers13174287
Vazquez A, Kamphorst JJ, Markert EK, Schug ZT, Tardito S, Gottlieb E. Cancer metabolism at a glance. J Cell Sci. 2016;129(18):3367–73.
pubmed: 27635066
pmcid: 6518336
doi: 10.1242/jcs.181016
Landor SK-J, Mutvei AP, Mamaeva V, Jin S, Busk M, Borra R, et al. Hypo-and hyperactivated Notch signaling induce a glycolytic switch through distinct mechanisms. Proc Natl Acad Sci. 2011;108(46):18814–9.
pubmed: 22065781
pmcid: 3219154
doi: 10.1073/pnas.1104943108
Vander Heiden MG, DeBerardinis RJ. Understanding the intersections between metabolism and cancer biology. Cell. 2017;168(4):657–69.
pubmed: 28187287
doi: 10.1016/j.cell.2016.12.039
Anderson G. Type I diabetes pathoetiology and pathophysiology: roles of the gut microbiome, pancreatic cellular interactions, and the ‘bystander’ activation of memory CD8+ T cells. Int J Mol Sci. 2023;24(4):3300.
pubmed: 36834709
pmcid: 9964837
doi: 10.3390/ijms24043300
Formentini L, Martínez-Reyes I, Cuezva JM. The mitochondrial bioenergetic capacity of carcinomas. IUBMB Life. 2010. https://doi.org/10.1002/iub.352 .
doi: 10.1002/iub.352
pubmed: 20552634
Yadav UP, Singh T, Kumar P, Sharma P, Kaur H, Sharma S, et al. Metabolic adaptations in cancer stem cells. Front Oncol. 2020;10:1010.
pubmed: 32670883
pmcid: 7330710
doi: 10.3389/fonc.2020.01010
Zheng J. Energy metabolism of cancer: Glycolysis versus oxidative phosphorylation. Oncol Lett. 2012;4(6):1151–7.
pubmed: 23226794
pmcid: 3506713
doi: 10.3892/ol.2012.928
Végran F, Boidot R, Michiels C, Sonveaux P, Feron O. Lactate influx through the endothelial cell monocarboxylate transporter MCT1 supports an NF-κB/IL-8 pathway that drives tumor angiogenesis. Can Res. 2011;71(7):2550–60.
doi: 10.1158/0008-5472.CAN-10-2828
Rothberg, J.M., K.M. Bailey, J.W. Wojtkowiak, Y. Ben-Nun, M. Bogyo, E. Weber, et al., Acid-mediated tumor proteolysis: contribution of cysteine cathepsins. Neoplasia, 2013. 15(10): p. 1125-IN9.
Hu Y, Lu W, Chen G, Wang P, Chen Z, Zhou Y, et al. K-rasG12V transformation leads to mitochondrial dysfunction and a metabolic switch from oxidative phosphorylation to glycolysis. Cell Res. 2012;22(2):399–412.
pubmed: 21876558
doi: 10.1038/cr.2011.145
Koppenol WH, Bounds PL, Dang CV. Otto Warburg’s contributions to current concepts of cancer metabolism. Nat Rev Cancer. 2011;11(5):325–37.
pubmed: 21508971
doi: 10.1038/nrc3038
Schiliro C, Firestein BL. Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation. 2021;10(5):1056.
Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod R, Zillhardt MR, et al. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med. 2011;17(11):1498–503.
pubmed: 22037646
pmcid: 4157349
doi: 10.1038/nm.2492
King, A., M. Selak, and, and E. Gottlieb, Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer. Oncogene, 2006. 25(34): p. 4675–4682.
Albadari, N., S. Deng, and W. Li, The transcriptional factors HIF-1 and HIF-2 and their novel inhibitors in cancer therapy. 2019. 14(7): p. 667–682.
Laurenti G, Tennant DA. Isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH), fumarate hydratase (FH): three players for one phenotype in cancer? Biochem Soc Trans. 2016;44(4):1111–6.
pubmed: 27528759
doi: 10.1042/BST20160099
Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim S-H, et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell. 2011;19(1):17–30.
pubmed: 21251613
pmcid: 3229304
doi: 10.1016/j.ccr.2010.12.014
Tarrado-Castellarnau M, de Atauri P, Cascante M. Oncogenic regulation of tumor metabolic reprogramming. Oncotarget. 2016;7(38):62726–53.
pubmed: 28040803
pmcid: 5308762
doi: 10.18632/oncotarget.10911
Harbeck N, Penault-Llorca F, Cortes J, Gnant M, Houssami N, Poortmans P, et al. Breast cancer Nature Reviews Disease Primers. 2019;5(1):66.
pubmed: 31548545
doi: 10.1038/s41572-019-0111-2
Dewan K, Mandal A. Surrogate molecular classification of breast carcinoma: A classification in need or a dilemma indeed. Oncology Journal of India. 2020;4(3):79–86.
doi: 10.4103/oji.oji_46_19
Wang Z, Jiang Q, Dong C. Metabolic reprogramming in triple-negative breast cancer. Cancer Biol Med. 2020;17(1):44–59.
pubmed: 32296576
pmcid: 7142847
doi: 10.20892/j.issn.2095-3941.2019.0210
Holloway, R.W. and P.A. Marignani, Targeting mTOR and Glycolysis in HER2-Positive Breast Cancer. Cancers (Basel), 2021. 13(12), 2922.
Cappelletti V, Iorio E, Miodini P, Silvestri M, Dugo M, Daidone MG. Metabolic footprints and molecular subtypes in breast cancer. Dis Markers. 2017;2017:7687851.
pubmed: 29434411
pmcid: 5757146
doi: 10.1155/2017/7687851
Shin E, Koo JS. Glucose metabolism and glucose transporters in breast cancer. Front Cell Dev Biol. 2021;9: 728759.
pubmed: 34552932
pmcid: 8450384
doi: 10.3389/fcell.2021.728759
Long J-P, Li X-N, Zhang F. Targeting metabolism in breast cancer: How far we can go? World journal of clinical oncology. 2016;7(1):122.
pubmed: 26862496
pmcid: 4734934
doi: 10.5306/wjco.v7.i1.122
Choi J, Jung W-H, Koo JS. Metabolism-related proteins are differentially expressed according to the molecular subtype of invasive breast cancer defined by surrogate immunohistochemistry. Pathobiology. 2013;80(1):41–52.
pubmed: 22832328
doi: 10.1159/000339513
Zhang, Y., Q. Li, Z. Huang, and B. Li, Targeting glucose metabolism enzymes in cancer treatment: current and emerging strategies. Cancers. 2022. 14(19), 4568.
Ko Y-H, Lin Z, Flomenberg N, Pestell RG, Howell A, Sotgia F, et al. Glutamine fuels a vicious cycle of autophagy in the tumor stroma and oxidative mitochondrial metabolism in epithelial cancer cells: implications for preventing chemotherapy resistance. Cancer Biol Ther. 2011;12(12):1085–97.
pubmed: 22236876
pmcid: 3335942
doi: 10.4161/cbt.12.12.18671
Ko B-H, Paik J-Y, Jung K-H, Lee K-H. 17β-Estradiol augments 18F-FDG uptake and glycolysis of T47D breast cancer cells via membrane-initiated rapid PI3K–Akt activation. J Nucl Med. 2010;51(11):1740–7.
pubmed: 20956467
doi: 10.2967/jnumed.110.074708
Fhu CW, Ali A. Fatty Acid Synthase: An Emerging Target in Cancer. Molecules. 2020;25(17):3935.
pubmed: 32872164
pmcid: 7504791
doi: 10.3390/molecules25173935
Iqbal MA, Bamezai RN. Resveratrol inhibits cancer cell metabolism by down regulating pyruvate kinase M2 via inhibition of mammalian target of rapamycin. PLoS ONE. 2012;7(5): e36764.
pubmed: 22574221
pmcid: 3344940
doi: 10.1371/journal.pone.0036764
Luo S, Jiang Y, Anfu Z, Zhao Y, Wu X, Li M, et al. Targeting hypoxia-inducible factors for breast cancer therapy: A narrative review. Front Pharmacol. 2022;13:1064661.
pubmed: 36532768
pmcid: 9751339
doi: 10.3389/fphar.2022.1064661
Miricescu D, Totan A, Stanescu-Spinu I-I, Badoiu SC, Stefani C, Greabu M. PI3K/AKT/mTOR signaling pathway in breast cancer: From molecular landscape to clinical aspects. Int J Mol Sci. 2020;22(1):173.
pubmed: 33375317
pmcid: 7796017
doi: 10.3390/ijms22010173
Kulkoyluoglu-Cotul E, Arca A, Madak-Erdogan Z. Crosstalk between estrogen signaling and breast cancer metabolism. Trends Endocrinol Metab. 2019;30(1):25–38.
pubmed: 30471920
doi: 10.1016/j.tem.2018.10.006
Lim, W., B. Mayer, and T. Pawson, Cell signaling. 2014: Taylor & Francis.
Bhaskar PT, Nogueira V, Patra KC, Jeon S-M, Park Y, Robey RB, et al. mTORC1 hyperactivity inhibits serum deprivation-induced apoptosis via increased hexokinase II and GLUT1 expression, sustained Mcl-1 expression, and glycogen synthase kinase 3β inhibition. Mol Cell Biol. 2009;29(18):5136–47.
pubmed: 19620286
pmcid: 2738274
doi: 10.1128/MCB.01946-08
Pande M, Bondy ML, Do K-A, Sahin AA, Ying J, Mills GB, et al. Association between germline single nucleotide polymorphisms in the PI3K-AKT-mTOR pathway, obesity, and breast cancer disease-free survival. Breast Cancer Res Treat. 2014;147(2):381–7.
pubmed: 25108739
pmcid: 4174407
doi: 10.1007/s10549-014-3081-9
Miller TW, Rexer BN, Garrett JT, Arteaga CL. Mutations in the phosphatidylinositol 3-kinase pathway: role in tumor progression and therapeutic implications in breast cancer. Breast Cancer Res. 2011;13(6):1–12.
doi: 10.1186/bcr3039
Sobral-Leite M, Salomon I, Opdam M, Kruger DT, Beelen KJ, van der Noort V, et al. Cancer-immune interactions in ER-positive breast cancers: PI3K pathway alterations and tumor-infiltrating lymphocytes. Breast Cancer Res. 2019;21(1):1–12.
doi: 10.1186/s13058-019-1176-2
Hudson CC, Liu M, Chiang GG, Otterness DM, Loomis DC, Kaper F, et al. Regulation of hypoxia-inducible factor 1α expression and function by the mammalian target of rapamycin. Mol Cell Biol. 2002;22(20):7004–14.
pubmed: 12242281
pmcid: 139825
doi: 10.1128/MCB.22.20.7004-7014.2002
Roberts D, Miyamoto S. Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy. Cell Death Differ. 2015;22(2):248–57.
pubmed: 25323588
doi: 10.1038/cdd.2014.173
Brown RS, Wahl RL. Overexpression of glut-1 glucose transporter in human breast cancer an immunohistochemical study. Cancer. 1993;72(10):2979–85.
pubmed: 8221565
doi: 10.1002/1097-0142(19931115)72:10<2979::AID-CNCR2820721020>3.0.CO;2-X
Gaude E, Frezza C. Defects in mitochondrial metabolism and cancer. Cancer Metabolism. 2014;2(1):1–9.
doi: 10.1186/2049-3002-2-10
Liu W-S, Chan S-H, Chang H-T, Li G-C, Tu Y-T, Tseng H-H, et al. Isocitrate dehydrogenase 1–snail axis dysfunction significantly correlates with breast cancer prognosis and regulates cell invasion ability. Breast Cancer Res. 2018;20(1):1–17.
doi: 10.1186/s13058-018-0953-7
Engelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer. 2009;9(8):550–62.
pubmed: 19629070
doi: 10.1038/nrc2664
Yang L, Hou Y, Yuan J, Tang S, Zhang H, Zhu Q, et al. Twist promotes reprogramming of glucose metabolism in breast cancer cells through PI3K/AKT and p53 signaling pathways. Oncotarget. 2015;6(28):25755.
pubmed: 26342198
pmcid: 4694864
doi: 10.18632/oncotarget.4697
Kotowski K, Rosik J, Machaj F, Supplitt S, Wiczew D, Jabłońska K, et al. Role of PFKFB3 and PFKFB4 in cancer: genetic basis, impact on disease development/progression, and potential as therapeutic targets. Cancers. 2021;13(4):909.
pubmed: 33671514
pmcid: 7926708
doi: 10.3390/cancers13040909
Liu Y, Wang R, Zhang L, Li J, Lou K, Shi B. The lipid metabolism gene FTO influences breast cancer cell energy metabolism via the PI3K/AKT signaling pathway. Oncol Lett. 2017;13(6):4685–90.
pubmed: 28599470
pmcid: 5452952
doi: 10.3892/ol.2017.6038
Tseng C-W, Kuo W-H, Chan S-H, Chan H-L, Chang K-J, Wang L-H. Transketolase regulates the metabolic switch to control breast cancer cell metastasis via the α-ketoglutarate signaling pathway. Can Res. 2018;78(11):2799–812.
doi: 10.1158/0008-5472.CAN-17-2906
Miao P, Sheng S, Sun X, Liu J, Huang G. Lactate dehydrogenase A in cancer: a promising target for diagnosis and therapy. IUBMB Life. 2013;65(11):904–10.
pubmed: 24265197
doi: 10.1002/iub.1216
He W, Miao FJ-P, Lin DC-H, Schwandner RT, Wang Z, Gao J, et al. Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors. Nature. 2004;429(6988):188–93.
pubmed: 15141213
doi: 10.1038/nature02488
Wise DR, Ward PS, Shay JE, Cross JR, Gruber JJ, Sachdeva UM, et al. Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of α-ketoglutarate to citrate to support cell growth and viability. Proc Natl Acad Sci. 2011;108(49):19611–6.
pubmed: 22106302
pmcid: 3241793
doi: 10.1073/pnas.1117773108
Mu X, Shi W, Xu Y, Xu C, Zhao T, Geng B, et al. Tumor-derived lactate induces M2 macrophage polarization via the activation of the ERK/STAT3 signaling pathway in breast cancer. Cell Cycle. 2018;17(4):428–38.
pubmed: 29468929
pmcid: 5927648
doi: 10.1080/15384101.2018.1444305
Zaugg, M., P.-H. Lou, E. Lucchinetti, M. Gandhi, and A.S. Clanachan, Postconditioning with Intralipid emulsion protects against reperfusion injury in post-infarct remodeled rat hearts by activation of ROS-Akt/Erk signaling. Translational Research, 2017. 186: p. 36–51. e2.
Tkach, M., C. Rosemblit, M.A. Rivas, C.J. Proietti, M.C. Díaz Flaqué, M.F. Mercogliano, et al., p42/p44 MAPK-mediated Stat3Ser727 phosphorylation is required for progestin-induced full activation of Stat3 and breast cancer growth. Endocr Relat Cancer, 2013. 20(2): p. 197–212.
Bromberg J. Stat proteins and oncogenesis. J Clin Investig. 2002;109(9):1139–42.
pubmed: 11994401
pmcid: 150969
doi: 10.1172/JCI0215617
Epling-Burnette P, Liu JH, Catlett-Falcone R, Turkson J, Oshiro M, Kothapalli R, et al. Inhibition of STAT3 signaling leads to apoptosis of leukemic large granular lymphocytes and decreased Mcl-1 expression. J Clin Investig. 2001;107(3):351–62.
pubmed: 11160159
pmcid: 199188
doi: 10.1172/JCI9940
Li R, Hebert JD, Lee TA, Xing H, Boussommier-Calleja A, Hynes RO, et al. Macrophage-secreted TNFα and TGFβ1 influence migration speed and persistence of cancer cells in 3D tissue culture via independent pathways. Can Res. 2017;77(2):279–90.
doi: 10.1158/0008-5472.CAN-16-0442
Yao A, Xiang Y, Si YR, Fan LJ, Li JP, Li H, et al. PKM2 promotes glucose metabolism through a let-7a-5p/Stat3/hnRNP-A1 regulatory feedback loop in breast cancer cells. J Cell Biochem. 2019;120(4):6542–54.
pubmed: 30368881
doi: 10.1002/jcb.27947
David CJ, Chen M, Assanah M, Canoll P, Manley JL. HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature. 2010;463(7279):364–8.
pubmed: 20010808
doi: 10.1038/nature08697
Li T, Kon N, Jiang L, Tan M, Ludwig T, Zhao Y, et al. Tumor suppression in the absence of p53-mediated cell-cycle arrest, apoptosis, and senescence. Cell. 2012;149(6):1269–83.
pubmed: 22682249
pmcid: 3688046
doi: 10.1016/j.cell.2012.04.026
Wang L, Zhang S, Wang X. The metabolic mechanisms of breast cancer metastasis. Front Oncol. 2021;10: 602416.
pubmed: 33489906
pmcid: 7817624
doi: 10.3389/fonc.2020.602416
Zhang C, Lin M, Wu R, Wang X, Yang B, Levine AJ, et al. Parkin, a p53 target gene, mediates the role of p53 in glucose metabolism and the Warburg effect. Proc Natl Acad Sci. 2011;108(39):16259–64.
pubmed: 21930938
pmcid: 3182683
doi: 10.1073/pnas.1113884108
Hsu C-C, Tseng L-M, Lee H-C. Role of mitochondrial dysfunction in cancer progression. Exp Biol Med. 2016;241(12):1281–95.
doi: 10.1177/1535370216641787
Karlsson, R., E. Pedersen, Z. Wang, and C. Brakebusch, Rho GTPase function in tumorigenesis. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 2009. 1796(2): p. 91–98.
Zhang C, Liu J, Liang Y, Wu R, Zhao Y, Hong X, et al. Tumour-associated mutant p53 drives the Warburg effect. Nat Commun. 2013;4(1):1–15.
doi: 10.1038/ncomms3935
Turgeon M-O, Perry NJ, Poulogiannis G. DNA damage, repair, and cancer metabolism. Front Oncol. 2018;8:15.
pubmed: 29459886
pmcid: 5807667
doi: 10.3389/fonc.2018.00015
Maréchal A, Zou L. DNA damage sensing by the ATM and ATR kinases. Cold Spring Harb Perspect Biol. 2013;5(9): a012716.
pubmed: 24003211
pmcid: 3753707
doi: 10.1101/cshperspect.a012716
Aird KM, Worth AJ, Snyder NW, Lee JV, Sivanand S, Liu Q, et al. ATM couples replication stress and metabolic reprogramming during cellular senescence. Cell Rep. 2015;11(6):893–901.
pubmed: 25937285
pmcid: 4431925
doi: 10.1016/j.celrep.2015.04.014
Turgeon M-O, Perry NJS, Poulogiannis G. DNA damage, repair, and cancer metabolism. Front Oncol. 2018. https://doi.org/10.3389/fonc.2018.00015 .
doi: 10.3389/fonc.2018.00015
pubmed: 29459886
pmcid: 5807667
Biswas DK, Iglehart JD. Linkage between EGFR family receptors and nuclear factor kappaB (NF-κB) signaling in breast cancer. J Cell Physiol. 2006;209(3):645–52.
pubmed: 17001676
doi: 10.1002/jcp.20785
Shi J, Wei PK. Interleukin-8: A potent promoter of angiogenesis in gastric cancer. Oncol Lett. 2016;11(2):1043–50.
pubmed: 26893688
doi: 10.3892/ol.2015.4035
Heidemann J, Ogawa H, Dwinell MB, Rafiee P, Maaser C, Gockel HR, et al. Angiogenic effects of interleukin 8 (CXCL8) in human intestinal microvascular endothelial cells are mediated by CXCR2*. J Biol Chem. 2003;278(10):8508–15.
pubmed: 12496258
doi: 10.1074/jbc.M208231200
Rizzo, M., L. Varnier, G. Pezzicoli, M. Pirovano, L. Cosmai, and C. Porta, IL-8 and its role as a potential biomarker of resistance to anti-angiogenic agents and immune checkpoint inhibitors in metastatic renal cell carcinoma. Frontiers in Oncology, 2022: p. 12, 4411.
Sudarshan S, Sourbier C, Kong H-S, Block K, Romero VV, Yang Y, et al. Fumarate hydratase deficiency in renal cancer induces glycolytic addiction and HIF-1α stabilization by glucose-dependent generation of reactive oxygen species. Mol Cell Biol. 2009;29(15):4080.
pubmed: 19470762
pmcid: 2715796
doi: 10.1128/MCB.00483-09
Shanmugasundaram K, Nayak B, Shim E-H, Livi CB, Block K, Sudarshan S. The oncometabolite fumarate promotes pseudohypoxia through noncanonical activation of NF-κB signaling. J Biol Chem. 2014;289(35):24691–9.
pubmed: 25028521
pmcid: 4148891
doi: 10.1074/jbc.M114.568162
Korherr C, Gille H, Schäfer R, Koenig-Hoffmann K, Dixelius J, Egland KA, et al. Identification of proangiogenic genes and pathways by high-throughput functional genomics: TBK1 and the IRF3 pathway. Proc Natl Acad Sci. 2006;103(11):4240–5.
pubmed: 16537515
pmcid: 1449677
doi: 10.1073/pnas.0511319103
Kamdje AHN, Etet PFS, Vecchio L, Muller JM, Krampera M, Lukong KE. Signaling pathways in breast cancer: therapeutic targeting of the microenvironment. Cell Signal. 2014;26(12):2843–56.
doi: 10.1016/j.cellsig.2014.07.034
Takebe N, Miele L, Harris PJ, Jeong W, Bando H, Kahn M, et al. Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update. Nat Rev Clin Oncol. 2015;12(8):445–64.
pubmed: 25850553
pmcid: 4520755
doi: 10.1038/nrclinonc.2015.61
Bruick RK, McKnight SL. A conserved family of prolyl-4-hydroxylases that modify HIF. Science. 2001;294(5545):1337–40.
pubmed: 11598268
doi: 10.1126/science.1066373
Funasaka T, Hogan V, Raz A. Phosphoglucose isomerase/autocrine motility factor mediates epithelial and mesenchymal phenotype conversions in breast cancer. Can Res. 2009;69(13):5349–56.
doi: 10.1158/0008-5472.CAN-09-0488
Cano A, Pérez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio MG, et al. The transcription factor snail controls epithelial–mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol. 2000;2(2):76–83.
pubmed: 10655586
doi: 10.1038/35000025
Shaw RJ, Kosmatka M, Bardeesy N, Hurley RL, Witters LA, DePinho RA, et al. The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc Natl Acad Sci. 2004;101(10):3329–35.
pubmed: 14985505
pmcid: 373461
doi: 10.1073/pnas.0308061100
Andrade-Vieira R, Xu Z, Colp P, Marignani PA. Loss of LKB1 expression reduces the latency of ErbB2-mediated mammary gland tumorigenesis, promoting changes in metabolic pathways. PLoS ONE. 2013;8(2): e56567.
pubmed: 23451056
pmcid: 3579833
doi: 10.1371/journal.pone.0056567
Zhang Z-G, Zhang H-S, Sun H-L, Liu H-Y, Liu M-Y, Zhou Z. KDM5B promotes breast cancer cell proliferation and migration via AMPK-mediated lipid metabolism reprogramming. Exp Cell Res. 2019;379(2):182–90.
pubmed: 30978340
doi: 10.1016/j.yexcr.2019.04.006
Boland M, Chourasia A, Macleod K. Mitochondrial Dysfunction in Cancer. Front Oncol. 2013. https://doi.org/10.3389/fonc.2013.00292 .
doi: 10.3389/fonc.2013.00292
pubmed: 24350057
pmcid: 3844930
Lamb R, Ablett MP, Spence K, Landberg G, Sims AH, Clarke RB. Wnt pathway activity in breast cancer sub-types and stem-like cells. PLoS ONE. 2013;8(7): e67811.
pubmed: 23861811
pmcid: 3701602
doi: 10.1371/journal.pone.0067811
Jeng K-S, Sheen I-S, Jeng W-J, Yu M-C, Hsiau H-I, Chang F-Y. High expression of Sonic Hedgehog signaling pathway genes indicates a risk of recurrence of breast carcinoma. Onco Targets Ther. 2014;7:79.
Hu J, Li T, Du S, Chen Y, Wang S, Xiong F, et al. The MAPK signaling pathway mediates the GPR91-dependent release of VEGF from RGC-5 cells. Int J Mol Med. 2015;36(1):130–8.
pubmed: 25936351
pmcid: 4494573
doi: 10.3892/ijmm.2015.2195
Huang Q, Cao H, Zhan L, Sun X, Wang G, Li J, et al. Mitochondrial fission forms a positive feedback loop with cytosolic calcium signaling pathway to promote autophagy in hepatocellular carcinoma cells. Cancer Lett. 2017;403:108–18.
pubmed: 28624623
doi: 10.1016/j.canlet.2017.05.034
Xie Q, Wu Q, Horbinski CM, Flavahan WA, Yang K, Zhou W, et al. Mitochondrial control by DRP1 in brain tumor initiating cells. Nat Neurosci. 2015;18(4):501–10.
pubmed: 25730670
pmcid: 4376639
doi: 10.1038/nn.3960
Ma Y, Wang L, Jia R. The role of mitochondrial dynamics in human cancers. Am J Cancer Res. 2020;10(5):1278.
pubmed: 32509379
pmcid: 7269774
Bushel PR, Ward J, Burkholder A, Li J, Anchang B. Mitochondrial-nuclear epistasis underlying phenotypic variation in breast cancer pathology. Sci Rep. 2022;12(1):1393.
pubmed: 35082309
pmcid: 8791930
doi: 10.1038/s41598-022-05148-4
Kim TW, Kim B, Kim JH, Kang S, Park S-B, Jeong G, et al. Nuclear-encoded mitochondrial MTO1 and MRPL41 are regulated in an opposite epigenetic mode based on estrogen receptor status in breast cancer. BMC Cancer. 2013;13(1):502.
pubmed: 24160266
pmcid: 4015551
doi: 10.1186/1471-2407-13-502
Chang S, Singh L, Thaker K, Abedi S, Singh MK, Patel TH, et al. Altered retrograde signaling patterns in breast cancer cells cybrids with H and J mitochondrial DNA haplogroups. Int J Mol Sci. 2022;23(12):6687.
pubmed: 35743133
pmcid: 9224519
doi: 10.3390/ijms23126687
El-Sahli S, Wang L. Cancer stem cell-associated pathways in the metabolic reprogramming of breast cancer. Int J Mol Sci. 2020;21(23):9125.
pubmed: 33266219
pmcid: 7730588
doi: 10.3390/ijms21239125
Oku Y, Nishiya N, Shito T, Yamamoto R, Yamamoto Y, Oyama C, et al. Small molecules inhibiting the nuclear localization of YAP/TAZ for chemotherapeutics and chemosensitizers against breast cancers. FEBS Open Bio. 2015;5:542–9.
pubmed: 26199863
pmcid: 4506957
doi: 10.1016/j.fob.2015.06.007
Ma J, Fan Z, Tang Q, Xia H, Zhang T, Bi F. Aspirin attenuates YAP and β-catenin expression by promoting β-TrCP to overcome docetaxel and vinorelbine resistance in triple-negative breast cancer. Cell Death Dis. 2020;11(7):530.
pubmed: 32661222
pmcid: 7359325
doi: 10.1038/s41419-020-2719-2
Sorrentino G, Ruggeri N, Specchia V, Cordenonsi M, Mano M, Dupont S, et al. Metabolic control of YAP and TAZ by the mevalonate pathway. Nat Cell Biol. 2014;16(4):357–66.
pubmed: 24658687
doi: 10.1038/ncb2936
Ishikawa T, Hosaka YZ, Beckwitt C, Wells A, Oltvai ZN, Warita K. Concomitant attenuation of HMG-CoA reductase expression potentiates the cancer cell growth-inhibitory effect of statins and expands their efficacy in tumor cells with epithelial characteristics. Oncotarget. 2018;9(50):29304.
pubmed: 30034619
pmcid: 6047681
doi: 10.18632/oncotarget.25448
Wang P, Gong Y, Guo T, Li M, Fang L, Yin S, et al. Activation of Aurora A kinase increases YAP stability via blockage of autophagy. Cell Death Dis. 2019;10(6):432.
pubmed: 31160567
pmcid: 6547697
doi: 10.1038/s41419-019-1664-4
Turkson J, Zhang S, Mora LB, Burns A, Sebti S, Jove R. A novel platinum compound inhibits constitutive Stat3 signaling and induces cell cycle arrest and apoptosis of malignant cells. J Biol Chem. 2005;280(38):32979–88.
pubmed: 16046414
doi: 10.1074/jbc.M502694200
Kim JW, Gautam J, Kim JE, Kim J, Kang KW. Inhibition of tumor growth and angiogenesis of tamoxifen-resistant breast cancer cells by ruxolitinib, a selective JAK2 inhibitor. Oncol Lett. 2019;17(4):3981–9.
pubmed: 30930994
pmcid: 6425385
Chen K-F, Tai W-T, Hsu C-Y, Huang J-W, Liu C-Y, Chen P-J, et al. Blockade of STAT3 activation by sorafenib derivatives through enhancing SHP-1 phosphatase activity. Eur J Med Chem. 2012;55:220–7.
pubmed: 22871485
doi: 10.1016/j.ejmech.2012.07.023
Srirangam A, Milani M, Mitra R, Guo Z, Rodriguez M, Kathuria H, et al. The human immunodeficiency virus protease inhibitor ritonavir inhibits lung cancer cells, in part, by inhibition of survivin. J Thorac Oncol. 2011;6(4):661–70.
pubmed: 21270666
pmcid: 3104055
doi: 10.1097/JTO.0b013e31820c9e3c
Park S, Chang C-Y, Safi R, Liu X, Baldi R, Jasper JS, et al. ERRα-regulated lactate metabolism contributes to resistance to targeted therapies in breast cancer. Cell Rep. 2016;15(2):323–35.
pubmed: 27050525
pmcid: 4833658
doi: 10.1016/j.celrep.2016.03.026
Wu T, Harder BG, Wong PK, Lang JE, Zhang DD. Oxidative stress, mammospheres and Nrf2–new implication for breast cancer therapy? Mol Carcinog. 2015;54(11):1494–502.
pubmed: 25154499
doi: 10.1002/mc.22202
Park S, Safi R, Liu X, Baldi R, Liu W, Liu J, et al. Inhibition of ERRα prevents mitochondrial pyruvate uptake exposing NADPH-generating pathways as targetable vulnerabilities in breast cancer. Cell Rep. 2019;27(12):3587.
pubmed: 31216477
pmcid: 6604861
doi: 10.1016/j.celrep.2019.05.066
Feldinger K, Kong A. Profile of neratinib and its potential in the treatment of breast cancer. Breast Cancer: Targets and Therapy. 2015;7:147.
pubmed: 26089701
Barry JB, Giguere V. Epidermal growth factor–induced signaling in breast cancer cells results in selective target gene activation by orphan nuclear receptor estrogen-related receptor α. Can Res. 2005;65(14):6120–9.
doi: 10.1158/0008-5472.CAN-05-0922
Madan B, Ke Z, Harmston N, Ho SY, Frois A, Alam J, et al. Wnt addiction of genetically defined cancers reversed by PORCN inhibition. Oncogene. 2016;35(17):2197–207.
pubmed: 26257057
doi: 10.1038/onc.2015.280
Furuya K, Sasaki A, Tsunoda Y, Tsuji M, Udaka Y, Oyamada H, et al. Eribulin upregulates miR-195 expression and downregulates Wnt3a expression in non-basal-like type of triple-negative breast cancer cell MDA-MB-231. Hum Cell. 2016;29:76–82.
pubmed: 26573286
doi: 10.1007/s13577-015-0126-2
Liu J, Pan S, Hsieh MH, Ng N, Sun F, Wang T, et al. Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proc Natl Acad Sci. 2013;110(50):20224–9.
pubmed: 24277854
pmcid: 3864356
doi: 10.1073/pnas.1314239110
Tam BY, Chiu K, Chung H, Bossard C, Nguyen JD, Creger E, et al. The CLK inhibitor SM08502 induces anti-tumor activity and reduces Wnt pathway gene expression in gastrointestinal cancer models. Cancer Lett. 2020;473:186–97.
pubmed: 31560935
doi: 10.1016/j.canlet.2019.09.009
Katoh M. Antibody-drug conjugate targeting protein tyrosine kinase 7, a receptor tyrosine kinase-like molecule involved in WNT and vascular endothelial growth factor signaling: effects on cancer stem cells, tumor microenvironment and whole-body homeostasis. Annals Transl Med. 2017;5(23):462.
doi: 10.21037/atm.2017.09.11
Fischer MM, Cancilla B, Yeung VP, Cattaruzza F, Chartier C, Murriel CL, et al. WNT antagonists exhibit unique combinatorial antitumor activity with taxanes by potentiating mitotic cell death. Sci Adv. 2017;3(6): e1700090.
pubmed: 28691093
pmcid: 5479655
doi: 10.1126/sciadv.1700090
Grzybowska-Szatkowska L, Ślaska B. Mitochondrial NADH dehydrogenase polymorphisms are associated with breast cancer in Poland. J Appl Genet. 2014;55(2):173–81.
pubmed: 24414975
pmcid: 3990858
doi: 10.1007/s13353-013-0190-9
Czarnecka AM, Klemba A, Krawczyk T, Zdrozny M, Arnold RS, Bartnik E, et al. Mitochondrial NADH-dehydrogenase polymorphisms as sporadic breast cancer risk factor. Oncol Rep. 2010;23(2):531–5.
pubmed: 20043118
Canter JA, Kallianpur AR, Parl FF, Millikan RC. Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African-American women. Can Res. 2005;65(17):8028–33.
doi: 10.1158/0008-5472.CAN-05-1428
Darvishi K, Sharma S, Bhat AK, Rai E, Bamezai R. Mitochondrial DNA G10398A polymorphism imparts maternal Haplogroup N a risk for breast and esophageal cancer. Cancer Lett. 2007;249(2):249–55.
pubmed: 17081685
doi: 10.1016/j.canlet.2006.09.005
Czarnecka AM, Krawczyk T, Plak K, Klemba A, Zdrozny M, Arnold RS, et al. Mitochondrial genotype and breast cancer predisposition. Oncol Rep. 2010;24(6):1521–34.
pubmed: 21042748
Tan D-J, Bai R-K, Wong L-JC. Comprehensive scanning of somatic mitochondrial DNA mutations in breast cancer. Can Res. 2002;62(4):972–6.
Gallardo ME, Moreno-Loshuertos R, López C, Casqueiro M, Silva J, Bonilla F, et al. m 6267G> A: a recurrent mutation in the human mitochondrial DNA that reduces cytochrome c oxidase activity and is associated with tumors. Hum Mutat. 2006;27(6):575–82.
pubmed: 16671096
doi: 10.1002/humu.20338
Girolimetti G, Marchio L, De Leo A, Mangiarelli M, Amato LB, Zanotti S, et al. Mitochondrial DNA analysis efficiently contributes to the identification of metastatic contralateral breast cancers. J Cancer Res Clin Oncol. 2021;147(2):507–16.
pubmed: 33236215
doi: 10.1007/s00432-020-03459-5
Grzybowska-Szatkowska L, Ślaska B, Rzymowska J, Brzozowska A, Floriańczyk B. Novel mitochondrial mutations in the ATP6 and ATP8 genes in patients with breast cancer. Mol Med Rep. 2014;10(4):1772–8.
pubmed: 25110199
pmcid: 4148381
doi: 10.3892/mmr.2014.2471
Kalia M. Personalized oncology: Recent advances and future challenges. Metabolism. 2013;62:S11–4.
pubmed: 22999010
doi: 10.1016/j.metabol.2012.08.016
Jayasekera LP, Ranasinghe R, Senathilake KS, Kotelawala JT, de Silva K, Abeygunasekara PH, et al. Mitochondrial genome in sporadic breast cancer: A case control study and a proteomic analysis in a Sinhalese cohort from Sri Lanka. PLoS ONE. 2023;18(2): e0281620.
pubmed: 36758048
pmcid: 9910733
doi: 10.1371/journal.pone.0281620
Jackson SE, Chester JD. Personalised cancer medicine. Int J Cancer. 2015;137(2):262–6.
pubmed: 24789362
doi: 10.1002/ijc.28940
Gambardella V, Tarazona N, Cejalvo JM, Lombardi P, Huerta M, Roselló S, et al. Personalized medicine: recent progress in cancer therapy. Cancers. 2020;12(4):1009.
pubmed: 32325878
pmcid: 7226371
doi: 10.3390/cancers12041009
Manzari MT, Shamay Y, Kiguchi H, Rosen N, Scaltriti M, Heller DA. Targeted drug delivery strategies for precision medicines. Nat Rev Mater. 2021;6(4):351–70.
pubmed: 34950512
pmcid: 8691416
doi: 10.1038/s41578-020-00269-6