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CBX7 binds the E-box to inhibit TWIST-1 function and inhibit tumorigenicity and metastatic potential

Oncogene volume 39, pages 3965–3979 (2020)Cite this article

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Abstract

Deaths from ovarian cancer usually occur when patients succumb to overwhelmingly numerous and widespread micrometastasis. Whereas epithelial–mesenchymal transition is required for epithelial ovarian cancer cells to acquire metastatic potential, the cellular phenotype at secondary sites and the mechanisms required for the establishment of metastatic tumors are not fully determined. Using in vitro and in vivo models we show that secondary epithelial ovarian cancer cells (sEOC) do not fully reacquire the molecular signature of the primary epithelial ovarian cancer cells from which they are derived. Despite displaying an epithelial morphology, sEOC maintains a high expression of the mesenchymal effector, TWIST-1. TWIST-1 is however transcriptionally nonfunctional in these cells as it is precluded from binding its E-box by the PcG protein, CBX7. Deletion of CBX7 in sEOC was sufficient to reactivate TWIST-1-induced transcription, prompt mesenchymal transformation, and enhanced tumorigenicity in vivo. This regulation allows secondary tumors to achieve an epithelial morphology while conferring the advantage of prompt reversal to a mesenchymal phenotype upon perturbation of CBX7. We also describe a subclassification of ovarian tumors based on CBX7 and TWIST-1 expression, which predicts clinical outcomes and patient prognosis.

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Fig. 1: Derivation of secondary epithelial ovarian cancer cells (sEOC) in vivo and in vitro.
Fig. 2: sEOC is molecularly distinct from the primary epithelial ovarian cancer cells.
Fig. 3: TWIST-1 is inactive in the sEOC.
Fig. 4: Loss of CBX7 in sEOC is sufficient to promote a mesenchymal phenotype and induce TWIST-1 target genes.
Fig. 5: CBX7 binds to mir-199A promoter region at or near the TWIST-1 binding site.
Fig. 6: Loss of CBX7 leads to enhanced metastatic potential and enhanced TWIST-1 activity in vivo.
Fig. 7: Loss of TWIST-1 leads to decreased metastatic potential.
Fig. 8: CBX7 is positive predictor of survival in TWIST-1pos patients.

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References

  1. Hildreth NG, Kelsey JL, LiVolsi VA, Fischer DB, Holford TR, Mostow ED, et al. An epidemiologic study of epithelial carcinoma of the ovary. Am J Epidemiol. 1981;114:398–405.

    Article  CAS  PubMed  Google Scholar 

  2. Heintz AP, Odicino F, Maisonneuve P, Quinn MA, Benedet JL, Creasman WT, et al. Carcinoma of the ovary. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet: Off organ Int Federation Gynaecol Obstet. 2006;95:S161–192.

    Article  Google Scholar 

  3. Goff BA, Balas C, Tenenbaum C. Ovarian cancer national alliance: a report of the 2012 Consensus Conference on Current Challenges in ovarian cancer. Gynecol Oncol. 2013;9–11.

  4. Kurman RJ, Shih IeM. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol. 2010;34:433–43.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Thrall MM, Gray HJ, Symons RG, Weiss NS, Flum DR, Goff BA. Trends in treatment of advanced epithelial ovarian cancer in the Medicare population. Gynecol Oncol. 2011;122:100–6.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Armstrong DK. Relapsed ovarian cancer: challenges and management strategies for a chronic disease. Oncologist. 2002;7:20–28.

    Article  CAS  PubMed  Google Scholar 

  7. Jelovac D, Armstrong DK. Recent progress in the diagnosis and treatment of ovarian cancer. CA Cancer J Clin. 2011;61:183–203.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Jarboe EA, Folkins AK, Drapkin R, Ince TA, Agoston ES, Crum CP. Tubal and ovarian pathways to pelvic epithelial cancer: a pathological perspective. Histopathology. 2008;53:127–38.

    Article  CAS  PubMed  Google Scholar 

  9. Naora H, Montell DJ. Ovarian cancer metastasis: integrating insights from disparate model organisms. Nat Rev Cancer. 2005;5:355–66.

    Article  CAS  PubMed  Google Scholar 

  10. Singh A, Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene. 2010;29:4741–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. 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 

  12. Vergara D, Merlot B, Lucot JP, Collinet P, Vinatier D, Fournier I, et al. Epithelial–mesenchymal transition in ovarian cancer. Cancer Lett. 2010;291:59–66.

    Article  CAS  PubMed  Google Scholar 

  13. Chen R, Alvero AB, Silasi DA, Steffensen KD, Mor G. Cancers take their Toll-the function and regulation of Toll-like receptors in cancer cells. Oncogene. 2008;27:225–33.

    Article  CAS  PubMed  Google Scholar 

  14. Ye X, Weinberg RA. Epithelial–mesenchymal plasticity: a central regulator of cancer progression. Trends Cell Biol. 2015;25:675–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zeisberg M, Neilson EG. Biomarkers for epithelial–mesenchymal transitions. J Clin Investig. 2009;119:1429–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Zheng X, Carstens JL, Kim J, Scheible M, Kaye J, Sugimoto H, et al. Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature. 2015;527:525–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jolly MK, Ware KE, Gilja S, Somarelli JA, Levine H. EMT and MET: necessary or permissive for metastasis? Mol Oncol. 2017;11:755–69.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Yao D, Dai C, Peng S. Mechanism of the mesenchymal–epithelial transition and its relationship with metastatic tumor formation. Mol Cancer Res. 2011;9:1608–20.

    Article  CAS  PubMed  Google Scholar 

  19. Jordan NV, Johnson GL, Abell AN. Tracking the intermediate stages of epithelial–mesenchymal transition in epithelial stem cells and cancer. Cell Cycle. 2011;10:2865–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lovisa S, LeBleu VS, Tampe B, Sugimoto H, Vadnagara K, Carstens JL, et al. Epithelial-to-mesenchymal transition induces cell cycle arrest and parenchymal damage in renal fibrosis. Nat Med. 2015;21:998–1009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ansieau S, Bastid J, Doreau A, Morel AP, Bouchet BP, Thomas C, et al. Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence. Cancer Cell. 2008;14:79–89.

    Article  CAS  PubMed  Google Scholar 

  22. Yin G, Chen R, Alvero AB, Fu HH, Holmberg J, Glackin C, et al. TWISTing stemness, inflammation and proliferation of epithelial ovarian cancer cells through MIR199A2/214. Oncogene. 2010;29:3545–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Glackin C, Winters K, Murray E, Murray S. Transcripts encoding the basic-helix-loop-helix factor twist are expressed in mouse embryos, cell lines, and adult tissues. Mol Cell Differ. 1994;2:309–28.

    CAS  Google Scholar 

  24. Carmona-Fontaine C, Theveneau E, Tzekou A, Tada M, Woods M, Page KM, et al. Complement fragment C3a controls mutual cell attraction during collective cell migration. Dev Cell. 2011;21:1026–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Comijn J, Berx G, Vermassen P, Verschueren K, van Grunsven L, Bruyneel E, et al. The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol Cell. 2001;7:1267–78.

    Article  CAS  PubMed  Google Scholar 

  26. Fabregat I, Malfettone A, Soukupova J. New insights into the crossroads between EMT and stemness in the context of cancer. J Clin Med. 2016;5.

  27. Willert K, Brown JD, Danenberg E, Duncan AW, Weissman IL, Reya T, et al. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature. 2003;423:448–52.

    Article  CAS  PubMed  Google Scholar 

  28. Gomez Tejeda Zanudo J, Guinn MT, Farquhar K, Szenk M, Steinway SN, Balazsi G, et al. Towards control of cellular decision-making networks in the epithelial-to-mesenchymal transition. Phys Biol. 2019;16:031002.

    Article  PubMed  CAS  Google Scholar 

  29. Kian W, Roisman LC, Peled N. Two are better than one on progression through MET mechanism for EGFR+ NSCLC patients. Transl Lung Cancer Res. 2018;7:S334–s335.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Yao D, Peng S, Dai C. The role of hepatocyte nuclear factor 4alpha in metastatic tumor formation of hepatocellular carcinoma and its close relationship with the mesenchymal–epithelial transition markers. BMC Cancer. 2013;13:432.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Leeb M, Pasini D, Novatchkova M, Jaritz M, Helin K, Wutz A. Polycomb complexes act redundantly to repress genomic repeats and genes. Genes Dev. 2010;24:265–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Leeb M, Wutz A. Polycomb complexes—genes make sense of host defense. Cell Cycle. 2010;9:2692–3.

    Article  CAS  PubMed  Google Scholar 

  33. Margueron R, Reinberg D. The Polycomb complex PRC2 and its mark in life. Nature. 2011;469:343–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Morey L, Helin K. Polycomb group protein-mediated repression of transcription. Trends Biochem Sci. 2010;35:323–32.

    Article  CAS  PubMed  Google Scholar 

  35. Yin G, Alvero AB, Craveiro V, Holmberg JC, Fu HH, Montagna MK, et al. Constitutive proteasomal degradation of TWIST-1 in epithelial-ovarian cancer stem cells impacts differentiation and metastatic potential. Oncogene. 2013;32:39–49.

    Article  CAS  PubMed  Google Scholar 

  36. Lee YB, Bantounas I, Lee DY, Phylactou L, Caldwell MA, Uney JB. Twist-1 regulates the miR-199a/214 cluster during development. Nucleic Acids Res. 2009;37:123–8.

    Article  CAS  PubMed  Google Scholar 

  37. Cheng GZ, Zhang WZ, Sun M, Wang Q, Coppola D, Mansour M, et al. Twist is transcriptionally induced by activation of STAT3 and mediates STAT3 oncogenic function. J Biol Chem. 2008;283:14665–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Chen R, Alvero AB, Silasi DA, Kelly MG, Fest S, Visintin I, et al. Regulation of IKKbeta by miR-199a affects NF-kappaB activity in ovarian cancer cells. Oncogene. 2008;27:4712–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Duan RS, Tang GB, Du HZ, Hu YW, Liu PP, Xu YJ, et al. Polycomb protein family member CBX7 regulates intrinsic axon growth and regeneration. Cell Death Differ. 2018;25:1598–611.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Federico A, Sepe R, Cozzolino F, Piccolo C, Iannone C, Iacobucci I, et al. The complex CBX7-PRMT1 has a critical role in regulating E-cadherin gene expression and cell migration. Biochim Biophys Acta Gene Regul Mech. 2019;1862:509–21.

    Article  CAS  PubMed  Google Scholar 

  41. Craveiro V, Yang-Hartwich Y, Holmberg JC, Joo WD, Sumi NJ, Pizzonia J, et al. Phenotypic modifications in ovarian cancer stem cells following Paclitaxel treatment. Cancer Med. 2013;2:751–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Baylies MK, Bate M. twist: a myogenic switch in Drosophila. Science. 1996;272:1481–4.

    Article  CAS  PubMed  Google Scholar 

  43. Bialek P, Kern B, Yang X, Schrock M, Sosic D, Hong N, et al. A twist code determines the onset of osteoblast differentiation. Dev Cell. 2004;6:423–35.

    Article  CAS  PubMed  Google Scholar 

  44. Seto ML, Lee SJ, Sze RW, Cunningham ML. Another TWIST on Baller-Gerold syndrome. Am J Med Genet. 2001;104:323–30.

    Article  CAS  PubMed  Google Scholar 

  45. Howard TD, Paznekas WA, Green ED, Chiang LC, Ma N, Ortiz de Luna RI, et al. Mutations in TWIST, a basic helix-loop-helix transcription factor, in Saethre–Chotzen syndrome. Nat Genet. 1997;15:36–41.

    Article  PubMed  Google Scholar 

  46. Glackin CA. Targeting the Twist and Wnt signaling pathways in metastatic breast cancer. Maturitas. 2014;79:48–51.

    Article  CAS  PubMed  Google Scholar 

  47. Glackin CA, Murray EJ, Murray SS. Doxorubicin inhibits differentiation and enhances expression of the helix-loop-helix genes Id and mTwi in mouse osteoblastic cells. Biochem Int. 1992;28:67–75.

    CAS  PubMed  Google Scholar 

  48. Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 2004;117:927–39.

    Article  CAS  PubMed  Google Scholar 

  49. Yang MH, Hsu DS, Wang HW, Wang HJ, Lan HY, Yang WH, et al. Bmi1 is essential in Twist1-induced epithelial–mesenchymal transition. Nat Cell Biol. 2010;12:982–92.

    Article  PubMed  CAS  Google Scholar 

  50. Shen CH, Wu JD, Jou YC, Cheng MC, Lin CT, Chen PC, et al. The correlation between TWIST, E-cadherin, and beta-catenin in human bladder cancer. J BUON Off J Balk Union Oncol. 2011;16:733–7.

    Google Scholar 

  51. Yang MH, Wu MZ, Chiou SH, Chen PM, Chang SY, Liu CJ, et al. Direct regulation of TWIST by HIF-1alpha promotes metastasis. Nat Cell Biol. 2008;10:295–305.

    Article  CAS  PubMed  Google Scholar 

  52. Yuen HF, Chan YP, Wong ML, Kwok WK, Chan KK, Lee PY, et al. Upregulation of Twist in oesophageal squamous cell carcinoma is associated with neoplastic transformation and distant metastasis. J Clin Pathol. 2007;60:510–4.

    Article  CAS  PubMed  Google Scholar 

  53. Tsai JH, Donaher JL, Murphy DA, Chau S, Yang J. Spatiotemporal regulation of epithelial–mesenchymal transition is essential for squamous cell carcinoma metastasis. Cancer Cell. 2012;22:725–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Mas G, Di Croce L. The role of Polycomb in stem cell genome architecture. Curr Opin Cell Biol. 2016;43:87–95.

    Article  CAS  PubMed  Google Scholar 

  55. Pallante P, Forzati F, Federico A, Arra C, Fusco A. Polycomb protein family member CBX7 plays a critical role in cancer progression. Am J Cancer Res. 2015;5:1594–601.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Scott CL, Gil J, Hernando E, Teruya-Feldstein J, Narita M, Martinez D, et al. Role of the chromobox protein CBX7 in lymphomagenesis. Proc Natl Acad Sci USA. 2007;104:5389–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Forzati F, Federico A, Pallante P, Abbate A, Esposito F, Malapelle U, et al. CBX7 is a tumor suppressor in mice and humans. J Clin Investig. 2012;122:612–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Bernard D, Martinez-Leal JF, Rizzo S, Martinez D, Hudson D, Visakorpi T, et al. CBX7 controls the growth of normal and tumor-derived prostate cells by repressing the Ink4a/Arf locus. Oncogene. 2005;24:5543–51.

    Article  CAS  PubMed  Google Scholar 

  59. Bao Z, Xu X, Liu Y, Chao H, Lin C, Li Z, et al. CBX7 negatively regulates migration and invasion in glioma via Wnt/beta-catenin pathway inactivation. Oncotarget. 2017;8:39048–63.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Pallante P, Sepe R, Federico A, Forzati F, Bianco M, Fusco A. CBX7 modulates the expression of genes critical for cancer progression. PLoS One. 2014;9:e98295.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Forzati F, Federico A, Pallante P, Colamaio M, Esposito F, Sepe R, et al. CBX7 gene expression plays a negative role in adipocyte cell growth and differentiation. Biol Open. 2014;3:871–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Forzati F, Federico A, Pallante P, Fedele M, Fusco A. Tumor suppressor activity of CBX7 in lung carcinogenesis. Cell Cycle. 2012;11:1888–91.

    Article  CAS  PubMed  Google Scholar 

  63. Wu W, Zhou X, Yu T, Bao Z, Zhi T, Jiang K, et al. The malignancy of miR-18a in human glioblastoma via directly targeting CBX7. Am J Cancer Res. 2017;7:64–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Yongyu Z, Lewei Y, Jian L, Yuqin S. MicroRNA-18a targets IRF2 and CBX7 to promote cell proliferation in hepatocellular carcinoma. Oncol Res. 2018;1327–34.

  65. Alvero AB, Chen R, Fu HH, Montagna M, Schwartz PE, Rutherford T, et al. Molecular phenotyping of human ovarian cancer stem cells unravels the mechanisms for repair and chemoresistance. Cell Cycle. 2009;8:158–66.

    Article  CAS  PubMed  Google Scholar 

  66. Alvero AB, Montagna MK, Chen R, Kim KH, Kyungjin K, Visintin I, et al. NV-128, a novel isoflavone derivative, induces caspase-independent cell death through the Akt/mammalian target of rapamycin pathway. Cancer. 2009;115:3204–16.

    Article  CAS  PubMed  Google Scholar 

  67. Alvero AB, O’Malley D, Brown D, Kelly G, Garg M, Chen W, et al. Molecular mechanism of phenoxodiol-induced apoptosis in ovarian carcinoma cells. Cancer. 2006;106:599–608.

    Article  CAS  PubMed  Google Scholar 

  68. Cardenas C, Montagna MK, Pitruzzello M, Lima E, Mor G, Alvero AB. Adipocyte microenvironment promotes Bclxl expression and confers chemoresistance in ovarian cancer cells. Apoptosis. 2017;22:558–69.

    Article  CAS  PubMed  Google Scholar 

  69. Kelly MG, Alvero AB, Chen R, Silasi DA, Abrahams VM, Chan S, et al. TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer. Cancer Res. 2006;66:3859–68.

    Article  CAS  PubMed  Google Scholar 

  70. Yang-Hartwich Y, Tedja R, Roberts CM, Goodner-Bingham J, Cardenas C, Gurea M, et al. p53-Pirh2 complex promotes Twist1 degradation and inhibits EMT. Mol Cancer Res. 2019;17:153–64.

    Article  CAS  PubMed  Google Scholar 

  71. Alvero AB, Heaton A, Lima E, Pitruzzello M, Sumi N, Yang-Hartwich Y, et al. TRX-E-002-1 induces c-Jun-dependent apoptosis in ovarian cancer stem cells and prevents recurrence in vivo. Mol Cancer Ther. 2016;15:1279–90.

    Article  CAS  PubMed  Google Scholar 

  72. Alvero AB, Kim D, Lima E, Sumi NJ, Lee JS, Cardenas C, et al. Novel approach for the detection of intraperitoneal micrometastasis using an ovarian cancer mouse model. Sci Rep. 2017;7:40989.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Pizzonia J, Holmberg J, Orton S, Alvero A, Viteri O, McLaughlin W, et al. Multimodality animal rotation imaging system (Mars) for in vivo detection of intraperitoneal tumors. Am J Reprod Immunol. 2012;67:84–90.

    Article  PubMed  Google Scholar 

  74. Kamsteeg M, Rutherford T, Sapi E, Hanczaruk B, Shahabi S, Flick M, et al. Phenoxodiol-an isoflavone analog-induces apoptosis in chemoresistant ovarian cancer cells. Oncogene. 2003;22:2611–20.

    Article  CAS  PubMed  Google Scholar 

  75. Tedja R, Roberts CM, Alvero AB, Cardenas C, Yang-Hartwich Y, Spadinger S, et al. Protein kinase Calpha-mediated phosphorylation of Twist1 at Ser-144 prevents Twist1 ubiquitination and stabilizes it. J Biol Chem. 2019;294:5082–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Yang-Hartwich Y, Soteras MG, Lin ZP, Holmberg J, Sumi N, Craveiro V, et al. p53 protein aggregation promotes platinum resistance in ovarian cancer. Oncogene. 2015;34:3605–16.

    Article  CAS  PubMed  Google Scholar 

  77. Alvero AB, Montagna MK, Sumi NJ, Joo WD, Graham E, Mor G. Multiple blocks in the engagement of oxidative phosphorylation in putative ovarian cancer stem cells: implication for maintenance therapy with glycolysis inhibitors. Oncotarget. 2014;5:8703–15.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F. Genome engineering using the CRISPR-Cas9 system. Nat Protoc. 2013;8:2281–308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study is supported in part by grants from NIH NCI R01CA199004 (GM), The National Natural Science Foundation of China No. 81572900 (GY), The National Key R&D Program of China, Stem Cell and Translation Research No. 2016YFA0102000 (GY), and Hunan Provincial Natural Science Foundation of China No. 2018JJ3820 (JL).

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Authors and Affiliations

  1. Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China

    Juanni Li, Yimin Li, Qing Xiao, Sai Zhang, Yaqi Gan, Xiaoying Wu & Gang Yin

  2. Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA

    Ayesha B. Alvero, Sudhakar Nuti, Roslyn Tedja, Cai M. Roberts, Mary Pitruzzello & Gil Mor

  3. C.S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA

    Gil Mor

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Contributions

JL: performance of experiments, data collection, data analysis, writing of paper; AA: design of experiment, development of experimental model systems, data analysis and interpretation, writing and editing paper; SN, RT, CR, MP, YL, QX, SZ, YG: performance of experiments, data collection, data analysis; GM and GY: conception, design of experiment, development of experimental model systems, data analysis and interpretation, writing and editing paper.

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Li, J., Alvero, A.B., Nuti, S. et al. CBX7 binds the E-box to inhibit TWIST-1 function and inhibit tumorigenicity and metastatic potential. Oncogene 39, 3965–3979 (2020). https://doi.org/10.1038/s41388-020-1269-5

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