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Here we report that hTERT gets SUMOylated by SUMO1 and polycomb protein CBX4 acts as the SUMO E3 ligase of hTERT. hTERT SUMOylation positively regulates its telomerase activity which can be inhibited by SENP3-mediated deSUMOylation. Interestingly, we have established a new role of hTERT SUMOylation in the repression of E-cadherin gene expression and consequent triggering on the epithelial-mesenchymal-transition (EMT) program in breast cancer cells. We also observed that catalytically active CBX4, leads to retention of hTERT\/ZEB1 complex onto E-cadherin promoter leading to its repression through hTERT-SUMOylation. Further through wound healing and invasion assays in breast cancer cells, we showed the tumor promoting ability of hTERT was significantly compromised upon overexpression of SUMO-defective mutant of hTERT. Thus our findings establish a new post-translational modification of hTERT which on one hand is involved in telomerase activity maintenance and on the other hand plays a crucial role in the regulation of gene expression thereby promoting migration and invasion of breast cancer cells.<\/jats:p>","DOI":"10.1042\/bcj20200359","type":"journal-article","created":{"date-parts":[[2020,9,14]],"date-time":"2020-09-14T11:16:45Z","timestamp":1600082205000},"page":"3803-3818","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["SUMO E3 ligase CBX4 regulates hTERT-mediated transcription of <i>CDH1<\/i> and promotes breast cancer cell migration and invasion"],"prefix":"10.1042","volume":"477","author":[{"given":"Sulagna","family":"Sanyal","sequence":"first","affiliation":[{"name":"Department of Biophysics, Molecular Biology and Bioinformatics, University of Calcutta, 92 A.P.C. Road, Kolkata 700009, India"},{"name":"Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1\/AF Bidhannagar, Kolkata 700064, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Payel","family":"Mondal","sequence":"additional","affiliation":[{"name":"Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1\/AF Bidhannagar, Kolkata 700064, India"},{"name":"Homi Bhaba National Institute, Mumbai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabyasachi","family":"Sen","sequence":"additional","affiliation":[{"name":"Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1\/AF Bidhannagar, Kolkata 700064, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumita","family":"Sengupta (Bandyopadhyay)","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Molecular Biology and Bioinformatics, University of Calcutta, 92 A.P.C. 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