Abstract
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 YAP5SA 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.
Keywords
Hippo pathway
P-body
PNRC1
YAP/TAZ
cancer biology
mouse
MeSH 主题词
Humans
YAP-Signaling Proteins/metabolism,genetics
Adaptor Proteins, Signal Transducing/metabolism,genetics
Transcription Factors/metabolism,genetics
Carcinogenesis/genetics
Cell Line, Tumor
Transcriptional Coactivator with PDZ-Binding Motif Proteins/metabolism
Trans-Activators/metabolism,genetics
Animals
Cell Proliferation
Colorectal Neoplasms/genetics,metabolism,pathology
Mice
Phosphoproteins/metabolism,genetics
Gene Expression Regulation, Neoplastic
Cell Movement
LIM Domain Proteins
化学物质
YAP-Signaling Proteins
Adaptor Proteins, Signal Transducing
Transcription Factors
YAP1 protein, human
Transcriptional Coactivator with PDZ-Binding Motif Proteins
WWTR1 protein, human
Trans-Activators
AJUBA protein, human
Phosphoproteins
LIM Domain Proteins
作者与单位
共 8 位作者，点击展开单位 / ORCID
Shen Xia
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 Xiang
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 YueGui
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 Zhujiang
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 Long
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 Wei
ORCID
State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.
Liu Yun
ORCID
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 Chen-Ying
ORCID
Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. | Shanghai Colorectal Cancer Research Center, Shanghai, China.
