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CtBP promotes metastasis of breast cancer through repressing cholesterol and activating TGF-β signaling

Oncogene volume 38, pages 2076–2091 (2019)Cite this article

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Abstract

Metastasis is the process through which the primary cancer cells spread beyond the primary tumor and disseminate to other organs. Most cancer patients die of metastatic disease. EMT is proposed to be the initial event associated with cancer metastasis and how it occurred is still a mystery. CtBP is known as a co-repressor abundantly expressed in many types of cancer and regulates genes involved in cancer initiation, progression, and metastasis. We found that CtBP regulates intracellular cholesterol homeostasis in breast cancer cells by forming a complex with ZEB1 and transcriptionally repressing SREBF2 expression. Importantly, CtBP repression of intracellular cholesterol abundance leads to increased EMT and cell migration. The reason is that cholesterol negatively regulates the stability of TGF-β receptors on the cell membrane. Interestingly, TGF-β is also capable of reducing intracellular cholesterol relying on the increased recruitment of ZEB1 and CtBP complex to SREBF2 promoter. Thus, we propose a feedback loop formed by CtBP, cholesterol, and TGF-β signaling pathway, through which TGF-β triggers the cascade that mobilizes the cancer cells for metastasis. Consistently, the intravenous injection of breast cancer cells with ectopically CtBP expression show increased lung metastasis depending on the reduction of intracellular cholesterol. Finally, we analyzed the public breast cancer datasets and found that CtBP expression negatively correlates with SREBF2 and HMGCR expressions. High expression of CtBP and low expression of SREBF2 and HMGCR significantly correlates with high EMT of the primary tumors.

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References

  1. Lambert AW, Pattabiraman DR, Weinberg RA. Emerging biological principles of metastasis. Cell. 2017;168:670–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Steeg PS. Targeting metastasis. Nat Rev Cancer. 2016;16:201–18.

    Article  CAS  PubMed  Google Scholar 

  3. Turajlic S, Swanton C. Metastasis as an evolutionary process. Science. 2016;352:169–75.

    Article  CAS  PubMed  Google Scholar 

  4. Valastyan S, Weinberg RA. Tumor metastasis: molecular insights and evolving paradigms. Cell. 2011;147:275–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Peinado H, Olmeda D, Cano A. Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer. 2007;7:415–28.

    Article  CAS  PubMed  Google Scholar 

  6. Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 2014;15:178–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Moustakas A, Heldin CH. Signaling networks guiding epithelial-mesenchymal transitions during embryogenesis and cancer progression. Cancer Sci. 2007;98:1512–20.

    Article  CAS  PubMed  Google Scholar 

  8. Sanchez-Tillo E, Liu Y, de Barrios O, Siles L, Fanlo L, Cuatrecasas M, et al. EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness. Cell Mol Life Sci. 2012;69:3429–56.

    Article  CAS  PubMed  Google Scholar 

  9. Massague J. TGFbeta in cancer. Cell. 2008;134:215–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Morrison CD, Parvani JG, Schiemann WP. The relevance of the TGF-beta paradox to EMT-MET programs. Cancer Lett. 2013;341:30–40.

    Article  CAS  PubMed  Google Scholar 

  11. Hall A. Rho GTPases and the actin cytoskeleton. Science. 1998;279:509–14.

    Article  CAS  PubMed  Google Scholar 

  12. Yang WH, Lan HY, Huang CH, Tai SK, Tzeng CH, Kao SY, et al. RAC1 activation mediates Twist1-induced cancer cell migration. Nat Cell Biol. 2012;14:366–74.

    Article  CAS  PubMed  Google Scholar 

  13. Renkawitz J, Schumann K, Weber M, Lammermann T, Pflicke H, Piel M, et al. Adaptive force transmission in amoeboid cell migration. Nat Cell Biol. 2009;11:1438–43.

    Article  CAS  PubMed  Google Scholar 

  14. Barcelo-Coblijn G, Martin ML, de Almeida RF, Noguera-Salva MA, Marcilla-Etxenike A, Guardiola-Serrano F, et al. Sphingomyelin and sphingomyelin synthase (SMS) in the malignant transformation of glioma cells and in 2-hydroxyoleic acid therapy. Proc Natl Acad Sci USA. 2011;108:19569–74.

    Article  CAS  PubMed  Google Scholar 

  15. Kojima K. Molecular aspects of the plasma membrane in tumor cells. Nagoya J Med Sci. 1993;56:1–18.

    CAS  PubMed  Google Scholar 

  16. Goluszko P, Nowicki B. Membrane cholesterol: a crucial molecule affecting interactions of microbial pathogens with mammalian cells. Infect Immun. 2005;73:7791–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zhao W, Prijic S, Urban BC, Tisza MJ, Zuo Y, Li L, et al. Candidate antimetastasis drugs suppress the metastatic capacity of breast cancer cells by reducing membrane fluidity. Cancer Res. 2016;76:2037–49.

    Article  CAS  PubMed  Google Scholar 

  18. Nelson ER, Wardell SE, Jasper JS, Park S, Suchindran S, Howe MK, et al. 27-Hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology. Science. 2013;342:1094–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hayes S, Chawla A, Corvera S. TGF beta receptor internalization into EEA1-enriched early endosomes: role in signaling to Smad2. J Cell Biol. 2002;158:1239–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Di Guglielmo GM, Le Roy C, Goodfellow AF, Wrana JL. Distinct endocytic pathways regulate TGF-beta receptor signalling and turnover. Nat Cell Biol. 2003;5:410–21.

    Article  PubMed  CAS  Google Scholar 

  21. Chen YG. Endocytic regulation of TGF-beta signaling. Cell Res. 2009;19:58–70.

    Article  PubMed  CAS  Google Scholar 

  22. Chinnadurai G. The transcriptional corepressor CtBP: a foe of multiple tumor suppressors. Cancer Res. 2009;69:731–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Pena C, Garcia JM, Garcia V, Silva J, Dominguez G, Rodriguez R, et al. The expression levels of the transcriptional regulators p300 and CtBP modulate the correlations between SNAIL, ZEB1, E-cadherin and vitamin D receptor in human colon carcinomas. Int J Cancer. 2006;119:2098–104.

    Article  CAS  PubMed  Google Scholar 

  24. Zhang Q, Wang SY, Fleuriel C, Leprince D, Rocheleau JV, Piston DW, et al. Metabolic regulation of SIRT1 transcription via a HIC1:CtBP corepressor complex. Proc Natl Acad Sci USA. 2007;104:829–33.

    Article  CAS  PubMed  Google Scholar 

  25. Deng H, Liu J, Deng Y, Han G, Shellman YG, Robinson SE, et al. CtBP1 is expressed in melanoma and represses the transcription of p16INK4a and Brca1. J Invest Dermatol. 2013;133:1294–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Deng Y, Deng H, Liu J, Han G, Malkoski S, Liu B, et al. Transcriptional down-regulation of Brca1 and E-cadherin by CtBP1 in breast cancer. Mol Carcinog. 2012;51:500–7.

    Article  CAS  PubMed  Google Scholar 

  27. Furusawa T, Moribe H, Kondoh H, Higashi Y. Identification of CtBP1 and CtBP2 as corepressors of zinc finger-homeodomain factor deltaEF1. Mol Cell Biol. 1999;19:8581–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Grooteclaes ML, Frisch SM. Evidence for a function of CtBP in epithelial gene regulation and anoikis. Oncogene. 2000;19:3823–8.

    Article  CAS  PubMed  Google Scholar 

  29. Lee S, Hong S, Kim S, Kang S. Ataxin-1 occupies the promoter region of E-cadherin in vivo and activates CtBP2-repressed promoter. Biochim Biophys Acta. 2011;1813:713–22.

    Article  CAS  PubMed  Google Scholar 

  30. Wang L, Zhou H, Wang Y, Cui G, Di LJ. CtBP maintains cancer cell growth and metabolic homeostasis via regulating SIRT4. Cell Death Dis. 2015;6:e1620.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Di LJ, Byun JS, Wong MM, Wakano C, Taylor T, Bilke S, et al. Genome-wide profiles of CtBP link metabolism with genome stability and epithelial reprogramming in breast cancer. Nat Commun. 2013;4:1449.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Di LJ, Fernandez AG, De Siervi A, Longo DL, Gardner K. Transcriptional regulation of BRCA1 expression by a metabolic switch. Nat Struct Mol Biol. 2010;17:1406–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Debiais-Delpech C, Godet J, Pedretti N, Bernard FX, Irani J, Cathelineau X et al. Expression patterns of candidate susceptibility genes HNF1beta and CtBP2 in prostate cancer: Association with tumor progression. Urol Oncol. 2013;32:426–32.

    Article  PubMed  CAS  Google Scholar 

  34. Wang R, Asangani IA, Chakravarthi BV, Ateeq B, Lonigro RJ, Cao Q, et al. Role of transcriptional corepressor CtBP1 in prostate cancer progression. Neoplasia. 2012;14:905–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Hamada F, Bienz M. The APC tumor suppressor binds to C-terminal binding protein to divert nuclear beta-catenin from TCF. Dev Cell. 2004;7:677–85.

    Article  CAS  PubMed  Google Scholar 

  36. Phelps RA, Chidester S, Dehghanizadeh S, Phelps J, Sandoval IT, Rai K, et al. A two-step model for colon adenoma initiation and progression caused by APC loss. Cell. 2009;137:623–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Bizama C, Benavente F, Salvatierra E, Gutierrez-Moraga A, Espinoza JA, Fernandez EA, et al. The low-abundance transcriptome reveals novel biomarkers, specific intracellular pathways and targetable genes associated with advanced gastric cancer. Int J Cancer. 2014;134:755–64.

    Article  CAS  PubMed  Google Scholar 

  38. Zhang XL, Huang CX, Zhang J, Inoue A, Zeng SE, Xiao SJ. CtBP1 is involved in epithelial-mesenchymal transition and is a potential therapeutic target for hepatocellular carcinoma. Oncol Rep. 2013;30:809–14.

    Article  CAS  PubMed  Google Scholar 

  39. Postigo AA, Dean DC. ZEB represses transcription through interaction with the corepressor CtBP. Proc Natl Acad Sci USA. 1999;96:6683–8.

    Article  CAS  PubMed  Google Scholar 

  40. van Grunsven LA, Michiels C, Van de Putte T, Nelles L, Wuytens G, Verschueren K, et al. Interaction between Smad-interacting protein-1 and the corepressor C-terminal binding protein is dispensable for transcriptional repression of E-cadherin. J Biol Chem. 2003;278:26135–45.

    Article  PubMed  CAS  Google Scholar 

  41. Sarrio D, Rodriguez-Pinilla SM, Hardisson D, Cano A, Moreno-Bueno G, Palacios J. Epithelial-mesenchymal transition in breast cancer relates to the basal-like phenotype. Cancer Res. 2008;68:989–97.

    Article  CAS  PubMed  Google Scholar 

  42. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 2005;102:15545–50.

    Article  CAS  PubMed  Google Scholar 

  43. Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest. 2002;109:1125–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Chen CL, Huang SS, Huang JS. Cholesterol modulates cellular TGF-beta responsiveness by altering TGF-beta binding to TGF-beta receptors. J Cell Physiol. 2008;215:223–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Maxfield FR, Wustner D. Intracellular cholesterol transport. J Clin Invest. 2002;110:891–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Maxfield FR, Wustner D. Analysis of cholesterol trafficking with fluorescent probes. Methods Cell Biol. 2012;108:367–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Ginestier C, Monville F, Wicinski J, Cabaud O, Cervera N, Josselin E, et al. Mevalonate metabolism regulates basal breast cancer stem cells and is a potential therapeutic target. Stem Cells. 2012;30:1327–37.

    Article  CAS  PubMed  Google Scholar 

  48. Mahammad S, Parmryd I. Cholesterol depletion using methyl-beta-cyclodextrin. Methods Mol Biol. 2015;1232:91–102.

    Article  CAS  PubMed  Google Scholar 

  49. Shimano H, Shimomura I, Hammer RE, Herz J, Goldstein JL, Brown MS, et al. Elevated levels of SREBP-2 and cholesterol synthesis in livers of mice homozygous for a targeted disruption of the SREBP-1 gene. J Clin Invest. 1997;100:2115–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Consortium EP, Bernstein BE, Birney E, Dunham I, Green ED, Gunter C, et al. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489:57–74.

    Article  CAS  Google Scholar 

  51. Drabsch Y, ten Dijke P. TGF-beta signalling and its role in cancer progression and metastasis. Cancer Metastas-Rev. 2012;31:553–68.

    Article  CAS  Google Scholar 

  52. Tan TZ, Miow QH, Miki Y, Noda T, Mori S, Huang RY, et al. Epithelial-mesenchymal transition spectrum quantification and its efficacy in deciphering survival and drug responses of cancer patients. EMBO Mol Med. 2014;6:1279–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Chiarugi P, Giannoni E. Anoikis: a necessary death program for anchorage-dependent cells. Biochem Pharmacol. 2008;76:1352–64.

    Article  CAS  PubMed  Google Scholar 

  54. Paliwal S, Ho N, Parker D, Grossman SR. CtBP2 promotes human cancer cell migration by transcriptional activation of Tiam1. Genes Cancer. 2012;3:481–90.

    PubMed  PubMed Central  Google Scholar 

  55. Zhang Q, Wang SY, Nottke AC, Rocheleau JV, Piston DW, Goodman RH. Redox sensor CtBP mediates hypoxia-induced tumor cell migration. Proc Natl Acad Sci USA. 2006;103:9029–33.

    Article  CAS  PubMed  Google Scholar 

  56. Zhou H, Zhang B, Zheng J, Yu M, Zhou T, Zhao K, et al. The inhibition of migration and invasion of cancer cells by graphene via the impairment of mitochondrial respiration. Biomaterials. 2014;35:1597–607.

    Article  CAS  PubMed  Google Scholar 

  57. Zadran S, Arumugam R, Herschman H, Phelps ME, Levine RD. Surprisal analysis characterizes the free energy time course of cancer cells undergoing epithelial-to-mesenchymal transition. Proc Natl Acad Sci USA. 2014;111:13235–40.

    Article  CAS  PubMed  Google Scholar 

  58. Dong C, Yuan T, Wu Y, Wang Y, Fan TW, Miriyala S, et al. Loss of FBP1 by Snail-mediated repression provides metabolic advantages in basal-like breast cancer. Cancer Cell. 2013;23:316–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Jiang L, Xiao L, Sugiura H, Huang X, Ali A, Kuro-o M, et al. Metabolic reprogramming during TGFbeta1-induced epithelial-to-mesenchymal transition. Oncogene. 2015;34:3908–16.

    Article  CAS  PubMed  Google Scholar 

  60. Halldorsson S, Rohatgi N, Magnusdottir M, Choudhary KS, Gudjonsson T, Knutsen E, et al. Metabolic re-wiring of isogenic breast epithelial cell lines following epithelial to mesenchymal transition. Cancer Lett. 2017;396:117–29.

    Article  CAS  PubMed  Google Scholar 

  61. Hamabe A, Konno M, Tanuma N, Shima H, Tsunekuni K, Kawamoto K, et al. Role of pyruvate kinase M2 in transcriptional regulation leading to epithelial-mesenchymal transition. Proc Natl Acad Sci USA. 2014;111:15526–31.

    Article  CAS  PubMed  Google Scholar 

  62. Ahmad A, Aboukameel A, Kong D, Wang Z, Sethi S, Chen W, et al. Phosphoglucose isomerase/autocrine motility factor mediates epithelial-mesenchymal transition regulated by miR-200 in breast cancer cells. Cancer Res. 2011;71:3400–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Funasaka T, Hogan V, Raz A. Phosphoglucose isomerase/autocrine motility factor mediates epithelial and mesenchymal phenotype conversions in breast cancer. Cancer Res. 2009;69:5349–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Jiang F, Ma S, Xue Y, Hou J, Zhang Y. LDH-A promotes malignant progression via activation of epithelial-to-mesenchymal transition and conferring stemness in muscle-invasive bladder cancer. Biochem Biophys Res Commun. 2016;469:985–92.

    Article  CAS  PubMed  Google Scholar 

  65. Liu K, Tang Z, Huang A, Chen P, Liu P, Yang J, et al. Glyceraldehyde-3-phosphate dehydrogenase promotes cancer growth and metastasis through upregulation of SNAIL expression. Int J Oncol. 2017;50:252–62.

    Article  CAS  PubMed  Google Scholar 

  66. Rios Garcia M, Steinbauer B, Srivastava K, Singhal M, Mattijssen F, Maida A, et al. Acetyl-CoA carboxylase 1-dependent protein acetylation controls breast cancer metastasis and recurrence. Cell Metab. 2017;26:842–55 e845.

    Article  CAS  PubMed  Google Scholar 

  67. Nath A, Li I, Roberts LR, Chan C. Elevated free fatty acid uptake via CD36 promotes epithelial-mesenchymal transition in hepatocellular carcinoma. Sci Rep. 2015;5:14752.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Kuzu OF, Noory MA, Robertson GP. The role of cholesterol in cancer. Cancer Res. 2016;76:2063–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Jacobs EJ, Newton CC, Thun MJ, Gapstur SM. Long-term use of cholesterol-lowering drugs and cancer incidence in a large United States cohort. Cancer Res. 2011;71:1763–71.

    Article  CAS  PubMed  Google Scholar 

  70. Cardwell CR, Hicks BM, Hughes C, Murray LJ. Statin use after colorectal cancer diagnosis and survival: a population-based cohort study. J Clin Oncol. 2014;32:3177–83.

    Article  PubMed  Google Scholar 

  71. Warita K, Warita T, Beckwitt CH, Schurdak ME, Vazquez A, Wells A, et al. Statin-induced mevalonate pathway inhibition attenuates the growth of mesenchymal-like cancer cells that lack functional E-cadherin mediated cell cohesion. Sci Rep. 2014;4:7593.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Chang TI, Kang HY, Kim KS, Lee SH, Nam BY, Paeng J, et al. The effect of statin on epithelial-mesenchymal transition in peritoneal mesothelial cells. PLoS One. 2014;9:e109628.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Yang T, Chen M, Sun T. Simvastatin attenuates TGF-beta1-induced epithelial-mesenchymal transition in human alveolar epithelial cells. Cell Physiol Biochem. 2013;31:863–74.

    Article  CAS  PubMed  Google Scholar 

  74. Zhuang L, Kim J, Adam RM, Solomon KR, Freeman MR. Cholesterol targeting alters lipid raft composition and cell survival in prostate cancer cells and xenografts. J Clin Invest. 2005;115:959–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Bjarnadottir O, Kimbung S, Johansson I, Veerla S, Jonsson M, Bendahl PO, et al. Global transcriptional changes following statin treatment in breast cancer. Clin Cancer Res. 2015;21:3402–11.

    Article  CAS  PubMed  Google Scholar 

  76. Chen CL, Liu IH, Fliesler SJ, Han X, Huang SS, Huang JS. Cholesterol suppresses cellular TGF-beta responsiveness: implications in atherogenesis. J Cell Sci. 2007;120:3509–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Izutsu K, Kurokawa M, Imai Y, Maki K, Mitani K, Hirai H. The corepressor CtBP interacts with Evi-1 to repress transforming growth factor beta signaling. Blood. 2001;97:2815–22.

    Article  CAS  PubMed  Google Scholar 

  78. Lin X, Liang YY, Sun B, Liang M, Shi Y, Brunicardi FC, et al. Smad6 recruits transcription corepressor CtBP to repress bone morphogenetic protein-induced transcription. Mol Cell Biol. 2003;23:9081–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Postigo AA, Depp JL, Taylor JJ, Kroll KL. Regulation of Smad signaling through a differential recruitment of coactivators and corepressors by ZEB proteins. EMBO J. 2003;22:2453–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Liu Y, Zhang N, Wang Y, Xu M, Liu N, Pang X, et al. Zinc finger E-box binding homeobox 1 promotes invasion and bone metastasis of small cell lung cancer in vitro and in vivo. Cancer Sci. 2012;103:1420–8.

    Article  CAS  PubMed  Google Scholar 

  81. Cancer Genome Atlas Research N. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474:609–15.

    Article  CAS  Google Scholar 

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Acknowledgements

The authors thank the animal facility, Single Cell & Gene expression Analysis Core of Faculty of Health Science for their support of this work.

Author contribution

ZZ, JL, YM, PL, and CZ performed the experiments and analyzed data; DH, LW, and YW analyzed data; HZ and KG discussed the manuscript; LW and DL, wrote the manuscript and supervised the research.

Funding

Funding

DL is supported by the Science and Technology Development Fund (FDCT) of Macao SAR (FDCT 014/2018/A1), the Multi-Year Research Grant from the University of Macau (MYRG2018–00158-FHS), and National Natural Science Foundation of China (grant no. 81772980). LW is supported by the Multi-Year Research Grant from the University of Macau (MYRG2016–00251-FHS). HZ is supported by National Natural Science Foundation of China (grant no. 81372911, 81772909). DH is supported by National Natural Science Foundation of China (grant no. 31701153).

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  1. Dapeng Hao

    Present address: Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA

Authors and Affiliations

  1. Cancer Center, Faculty of Health Sciences, University of Macau, Macau, China

    Zhiqiang Zhao, Dapeng Hao, Li Wang, Jingjing Li, Yuan Meng, Peipei Li, Yuan Wang, Chao Zhang & Li-jun Di

  2. Metabolomics Core, Faculty of Health Sciences, University of Macau, Macau, China

    Li Wang

  3. Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, China

    Haisheng Zhou

  4. Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, USA

    Kevin Gardner

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Zhao, Z., Hao, D., Wang, L. et al. CtBP promotes metastasis of breast cancer through repressing cholesterol and activating TGF-β signaling. Oncogene 38, 2076–2091 (2019). https://doi.org/10.1038/s41388-018-0570-z

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