The Hippo signaling pathway maintains organ size and tissue homeostasis via orchestration of cell proliferation and apoptosis. How this pathway triggers cell apoptosis remains largely unexplored. Here, we identify NR4A1 as a target of the Hippo pathway that mediates the pro-apoptotic and anti-tumor effects of the Hippo pathway whereby YAP regulates the transcription, phosphorylation, and mitochondrial localization of NR4A1. NR4A1, in turn, functions as a feedback inhibitor of YAP to promote its degradation, thereby inhibiting the function of YAP during liver regeneration and tumorigenesis. Our studies elucidate a regulatory loop between NR4A1 and YAP to coordinate Hippo signaling activity during liver regeneration and tumorigenesis and highlight NR4A1 as a marker of Hippo signaling, as well as a therapeutic target for hepatocellular carcinoma.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.celrep.2020.108284 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
DNA-damage orchestrates self-renewal and differentiation via reciprocal p53 family and Hippo/Wnt/TGF-β pathway activation in embryonic stem cells.
Cell Mol Life Sci
January 2025
Cam-Su Genomic Resource Center, Medical College of Soochow University, Suzhou, China.
The mechanism by which DNA-damage affects self-renewal and pluripotency remains unclear. DNA damage and repair mechanisms have been largely elucidated in mutated cancer cells or simple eukaryotes, making valid interpretations on early development difficult. Here we show the impact of ionizing irradiation on the maintenance and early differentiation of mouse embryonic stem cells (ESCs).
View Article and Find Full Text PDFcircTP63-N suppresses the proliferation and metastasis of nasopharyngeal carcinoma via engaging with HSP90AB1 to modulate the YAP1/Hippo signaling pathway.
Sci China Life Sci
December 2024
NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410078, China.
Circular RNAs (circRNAs) play pivotal roles in the development and progression of various diseases, including malignant tumors. However, the biological functions and the underlying mechanisms of many circRNAs remain elusive. In this study, we identified a novel circRNA, circTP63-N, generated through the splicing of exons 2-4 of the TP63 gene in nasopharyngeal carcinoma (NPC).
View Article and Find Full Text PDFNicotine enhances the stemness and tumorigenicity in intestinal stem cells via Hippo-YAP/TAZ and Notch signal pathway.
Elife
January 2025
Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Cigarette smoking is a well-known risk factor inducing the development and progression of various diseases. Nicotine (NIC) is the major constituent of cigarette smoke. However, knowledge of the mechanism underlying the NIC-regulated stem cell functions is limited.
View Article and Find Full Text PDFEpigenetic silencing of promotes laryngeal squamous cell carcinoma development by inhibiting the Hippo pathway.
Oncol Rep
February 2025
Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Laryngeal squamous cell carcinoma (LSCC), which represents a significant proportion of head and neck squamous cell carcinoma cases, is often diagnosed at advanced stages, underscoring the urgent need for effective biomarkers and therapeutic targets. Junctional adhesion molecule 3 () is implicated in various types of cancer; however, its role in LSCC remains unclear. Therefore, the present study aimed to investigate the epigenetic regulation and tumor‑suppressive functions and mechanisms of in LSCC.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!