Sirtuin 7 Promotes Mesenchymal to Epithelial Transition by β-Catenin Redistribution and Stabilization

Shashi Kiran; Manjari Kiran; Gayatri Ramakrishna

doi:10.3389/fonc.2020.00740

Sirtuin 7 Promotes Mesenchymal to Epithelial Transition by β-Catenin Redistribution and Stabilization

Front Oncol. 2020 Jun 23:10:740. doi: 10.3389/fonc.2020.00740. eCollection 2020.

Authors

Shashi Kiran^{1

2}, Manjari Kiran^{2

3}, Gayatri Ramakrishna⁴

Affiliations

¹ Department of Biochemistry, University of Hyderabad, Hyderabad, India.
² Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
³ Department of Systems & Computational Biology, University of Hyderabad, Hyderabad, India.
⁴ Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.

Abstract

SIRT7 belongs to the family of "NAD+ dependent deacetylases" called Sirtuins. In the present work we report a novel role of SIRT7 in regulating cellular polarity. SIRT7 overexpression in immortalized mouse fibroblasts (NIH3T3) induced epithelial transition. This transition was accompanied by typical N- to E- cadherin transition, stabilization of β-catenin, and the downregulation of transcription factors responsible for maintenance of mesenchymal phenotype (Snail, Slug, and Zeb1). Interestingly, a subpopulation of cells overexpressing SIRT7 exhibited an intermediate stage between mesenchymal and epithelial characters. Transformed epithelial cells showed a loss of heterochromatisation as evidenced by a loss of HP1α and H3K9 dimethylation staining. In conclusion, we report a role of SIRT7 in mesenchymal cells, which may have implications for health and disease.

Keywords: MET; SIRT7; Snail; cadherin; β-catenin.