دورية أكاديمية

Microrchidia 2/histone deacetylase 1 complex regulates E-cadherin gene expression and function.

التفاصيل البيبلوغرافية
العنوان: Microrchidia 2/histone deacetylase 1 complex regulates E-cadherin gene expression and function.
المؤلفون: Thomas, Liz, Chutani, Namita, R., Krishna, Nair, Asha S., Yellapu, Nanda Kumar, Karyala, Prashanthi, Pakala, Suresh B.
المصدر: Biochemical Journal; Oct2023, Vol. 480 Issue 20, p1675-1691, 17p
مصطلحات موضوعية: CADHERINS, CANCER cell migration, GENE expression, CANCER cell proliferation, GLUCOSE metabolism
مستخلص: 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. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:02646021
DOI:10.1042/BCJ20230304