Microrchidia 2/histone deacetylase 1 complex regulates E-cadherin gene expression and function.
| Autor: | Thomas L; Biology Division, Indian Institute of Science Education and Research (IISER) Tirupati, Mangalam, Tirupati 517 507, India., Chutani N; Biology Division, Indian Institute of Science Education and Research (IISER) Tirupati, Mangalam, Tirupati 517 507, India., R K; Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Trivandrum, Kerala 695 014, India., Nair AS; Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Trivandrum, Kerala 695 014, India., Yellapu NK; Department of Biostatistics & Data Science, University of Kansas Medical Centre, 3901 Rainbow Boulevard, Kansas City, KS 66160, U.S.A., Karyala P; Department of Biotechnology, Faculty of Life and Allied Health Sciences, Ramaiah University of Applied Sciences, Bengaluru 560054, India., Pakala SB; Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad 500 046, India. |
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| Jazyk: | angličtina |
| Zdroj: | The Biochemical journal [Biochem J] 2023 Oct 31; Vol. 480 (20), pp. 1675-1691. |
| DOI: | 10.1042/BCJ20230304 |
| Abstrakt: | Although Microrchidia 2 (MORC2) is widely overexpressed in human malignancies and linked to cancer cell proliferation, metabolism, and metastasis, the mechanism of action of MORC2 in cancer cell migration and invasion is yet undeciphered. Here, we identified for the first time that MORC2, a chromatin remodeler, regulates E-cadherin expression and, subsequently regulates breast cancer cell migration and invasion. We observed a negative correlation between the expression levels of MORC2 and E-cadherin in breast cancer. Furthermore, the overexpression of MORC2 resulted in decreased expression levels of E-cadherin. In addition, co-immunoprecipitation and chromatin immunoprecipitation assays revealed that MORC2 interacts with HDAC1 and gets recruited onto the E-cadherin promoter to inhibit its transcription, thereby suppress its expression. Consequently, knockdown of HDAC1 in MORC2-overexpressing cells led to reduced cancer cell migration and invasion. Interestingly, we noticed that MORC2-regulated glucose metabolism via c-Myc, and LDHA, also modulates the expression of E-cadherin. Collectively, these results demonstrate for the first time a mechanistic role for MORC2 as an upstream regulator of E-cadherin expression and its associated functions in breast cancer. (© 2023 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.) |
| Databáze: | MEDLINE |
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