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المؤلفEl-Hajjar, Layal
المؤلفSaliba, Jessica
المؤلفKaram, Mario
المؤلفShaito, Abdullah
المؤلفEl Hajj, Hiba
المؤلفEl-Sabban, Marwan
تاريخ الإتاحة2023-02-13T05:49:59Z
تاريخ النشر2023-02-03
اسم المنشورIJMS
المعرّفhttp://dx.doi.org/10.3390/ijms24032958
الاقتباسEl-Hajjar, L.; Saliba, J.; Karam, M.; Shaito, A.; El Hajj, H.; El-Sabban, M. Ubiquitin-Related Modifier 1 (URM-1) Modulates Cx43 in Breast Cancer Cell Lines. Int. J. Mol. Sci. 2023, 24, 2958. https://doi.org/10.3390/ijms24032958
معرّف المصادر الموحدhttp://hdl.handle.net/10576/40002
الملخصGap-junction-forming connexins are exquisitely regulated by post-translational modifications (PTMs). In particular, the PTM of connexin 43 (Cx43), a tumor suppressor protein, regulates its turnover and activity. Here, we investigated the interaction of Cx43 with the ubiquitin-related modifier 1 (URM-1) protein and its impact on tumor progression in two breast cancer cell lines, highly metastatic triple-negative MDA-MB-231 and luminal breast cancer MCF-7 cell lines. To evaluate the subsequent modulation of Cx43 levels, URM-1 was downregulated in these cells. The transcriptional levels of epithelial-to-mesenchymal transition (EMT) markers and the metastatic phenotype were assessed. We demonstrated that Cx43 co-localizes and interacts with URM-1, and URMylated Cx43 was accentuated upon cellular stress. The significant upregulation of small ubiquitin-like modifier-1 (SUMO-1) was also observed. In cells with downregulated URM-1, Cx43 expression significantly decreased, and SUMOylation by SUMO-1 was affected. The concomitant expression of EMT markers increased, leading to increased proliferation, migration, and invasion potential. Inversely, the upregulation of URM-1 increased Cx43 expression and reversed EMT-induced processes, underpinning a role for this PTM in the observed phenotypes. This study proposes that the URMylation of Cx43 in breast cancer cells regulates its tumor suppression properties and contributes to breast cancer cell malignancy.
راعي المشروعThis research was funded by grants from the Medical Practice Plan and the University Research Board at the Faculty of Medicine at the American University of Beirut, in addition to a grant from the Lebanese National Council for Scientific Research.
اللغةen
الناشرMDPI
الموضوعCx43
URM-1
breast cancer
epithelial-to-mesenchymal transition
post-translational modification
العنوانUbiquitin-Related Modifier 1 (URM-1) Modulates Cx43 in Breast Cancer Cell Lines.
النوعArticle
رقم العدد3
رقم المجلد24
ESSN1422-0067
dc.accessType Open Access


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