KAT8 acetylation-controlled lipolysis affects the invasive and migratory potential of colorectal cancer cells

• Published in: Cell death & disease Vol. 14; no. 2; pp. 164 - 13
• Main Authors: Qiu, Bingquan, Li, Shen, Li, Meiting, Wang, Shuo, Mu, Guanqun, Chen, Keyu, Wang, Meng, Zhu, Wei-guo, Wang, Weibin, Wang, Jiadong, Li, Ziyu, Yang, Jichun, Yang, Yang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.02.2023; Springer Nature B.V; Nature Publishing Group
• Subjects: 14/19; 38/39; 38/77; 38/89; 38/90; 42/109; 631/337/176; 631/337/458/1275; 82/1; 82/58; 82/80; 82/83; Acetylation; Antibodies; Biochemistry; Biomedical and Life Sciences; Biosynthesis; Cancer; Cancer therapies; Cell Biology; Cell Culture; Cell growth; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Deacetylation; DNA-directed RNA polymerase; Epigenetics; Fatty acids; Fatty-acid synthase; Gene expression; Glycerol; Histone acetyltransferase; Histone Acetyltransferases; Humans; Immunology; Invasiveness; Laboratories; Life Sciences; Lipase; Lipid Metabolism; Lipids; Lipogenesis; Lipolysis; Metabolism; Proteins; Science; Sirtuins - genetics
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-023-05582-w

Epigenetic mechanisms involved in gene expression play an essential role in various cellular processes, including lipid metabolism. Lysine acetyltransferase 8 (KAT8), a histone acetyltransferase, has been reported to mediate de novo lipogenesis by acetylating fatty acid synthase. However, the effect of KAT8 on lipolysis is unclear. Here, we report a novel mechanism of KAT8 on lipolysis involving in its acetylation by general control non-repressed protein 5 (GCN5) and its deacetylation by Sirtuin 6 (SIRT6). KAT8 acetylation at K168/175 residues attenuates the binding activity of KAT8 and inhibits the recruitment of RNA pol II to the promoter region of the lipolysis-related genes adipose triglyceride lipase ( ATGL ) and hormone-sensitive lipase ( HSL ), subsequently down-regulating lipolysis to affect the invasive and migratory potential of colorectal cancer cells. Our findings uncover a novel mechanism that KAT8 acetylation-controlled lipolysis affects invasive and migratory potential in colorectal cancer cells.