YAP/TAZ enhances P-body formation to promote tumorigenesis.

Autor: Shen X; Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Shanghai Colorectal Cancer Research Center, Shanghai, China., Peng X; Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Shanghai Colorectal Cancer Research Center, Shanghai, China., Guo Y; Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Shanghai Colorectal Cancer Research Center, Shanghai, China., Dai Z; Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Shanghai Colorectal Cancer Research Center, Shanghai, China., Cui L; Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Shanghai Colorectal Cancer Research Center, Shanghai, China., Yu W; State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China., Liu Y; Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Shanghai Colorectal Cancer Research Center, Shanghai, China., Liu CY; Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Shanghai Colorectal Cancer Research Center, Shanghai, China.
Jazyk: angličtina
Zdroj: ELife [Elife] 2024 Jul 24; Vol. 12. Date of Electronic Publication: 2024 Jul 24.
DOI: 10.7554/eLife.88573
Abstrakt: The role of processing bodies (P-bodies) in tumorigenesis and tumor progression is not well understood. Here, we showed that the oncogenes YAP/TAZ promote P-body formation in a series of cancer cell lines. Mechanistically, both transcriptional activation of the P-body-related genes SAMD4A, AJUBA , and WTIP and transcriptional suppression of the tumor suppressor gene PNRC1 are involved in enhancing the effects of YAP/TAZ on P-body formation in colorectal cancer (CRC) cells. By reexpression of PNRC1 or knockdown of P-body core genes ( DDX6, DCP1A, and LSM14A ), we determined that disruption of P-bodies attenuates cell proliferation, cell migration, and tumor growth induced by overexpression of YAP 5SA in CRC. Analysis of a pancancer CRISPR screen database (DepMap) revealed co-dependencies between YAP/TEAD and the P-body core genes and correlations between the mRNA levels of SAMD4A, AJUBA, WTIP, PNRC1, and YAP target genes. Our study suggests that the P-body is a new downstream effector of YAP/TAZ, which implies that reexpression of PNRC1 or disruption of P-bodies is a potential therapeutic strategy for tumors with active YAP.
Competing Interests: XS, XP, YG, ZD, LC, WY, YL, CL No competing interests declared
(© 2023, Shen, Peng, Guo et al.)
Databáze: MEDLINE