Ubiquitin-like protein FAT10 promotes osteosarcoma growth by modifying the ubiquitination and degradation of YAP1.

Abstract

Osteosarcoma is a common malignancy of the bone tissue. The rapid growth exhibited by this cancer is a primary challenge in its treatment. In many types of cancers, FAT10, a ubiquitin-like protein, is involved in several biological activities, especially cell proliferation. Herein, we demonstrate that FAT10 plays a vital role in tumorigenesis and is overexpressed in tumor tissues compared to its expression in adjacent normal tissues. Functional assays revealed that knockdown of FAT10 expression significantly repressed the proliferation of osteosarcoma in vitro and in vivo. Furthermore, our results indicate that FAT10 exhibits oncogenic functions by regulating the level of YAP1, a key protein of the Hippo/YAP signaling pathway, and a significant positive correlation exists between the levels of FAT10 and YAP1. Further analysis showed that FAT10-induced growth of osteosarcoma cells is dependent on YAP1. Mechanistically, FAT10 stabilizes YAP1 expression by regulating its ubiquitination and degradation. Taken together, our results link the two drivers of cell growth in osteosarcoma and reveal a novel pathway for FAT10 regulation. We provide new evidence for the biological and clinical significance of FAT10 as a potential biomarker for osteosarcoma.

• Authors: Xuan Yi, Xueqiang Deng, Yanzhi Zhao, Binbin Deng, Jianyong Deng, Huimin Fan, Yunyan Du, Liang Hao
• Journal: Experimental cell research (Exp Cell Res) Vol. 387 Issue 2 Pg. 111804 (02 15 2020) ISSN: 1090-2422 [Electronic] United States
• PMID: 31877302 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Adaptor Proteins, Signal Transducing
• Biomarkers
• Transcription Factors
• UBD protein, human
• Ubiquitins
• YAP-Signaling Proteins
• YAP1 protein, human

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Biomarkers (metabolism)
• Carcinogenesis (metabolism)
• Cell Line
• Cell Line, Tumor
• Cell Proliferation (physiology)
• Humans
• Osteosarcoma (metabolism, pathology)
• Signal Transduction (physiology)
• Transcription Factors (metabolism)
• Ubiquitination (physiology)
• Ubiquitins (metabolism)
• YAP-Signaling Proteins