New insights into fibrotic signaling in renal cell carcinoma

Front Cell Dev Biol. 2023 Feb 21:11:1056964. doi: 10.3389/fcell.2023.1056964. eCollection 2023.

Abstract

Fibrotic signaling plays a pivotal role in the development and progression of solid cancers including renal cell carcinoma (RCC). Intratumoral fibrosis (ITF) and pseudo-capsule (PC) fibrosis are significantly correlated to the disease progression of renal cell carcinoma. Targeting classic fibrotic signaling processes such as TGF-β signaling and epithelial-to-mesenchymal transition (EMT) shows promising antitumor effects both preclinically and clinically. Therefore, a better understanding of the pathogenic mechanisms of fibrotic signaling in renal cell carcinoma at molecular resolution can facilitate the development of precision therapies against solid cancers. In this review, we systematically summarized the latest updates on fibrotic signaling, from clinical correlation and molecular mechanisms to its therapeutic strategies for renal cell carcinoma. Importantly, we examined the reported fibrotic signaling on the human renal cell carcinoma dataset at the transcriptome level with single-cell resolution to assess its translational potential in the clinic.

Keywords: TGF-β; cancer-associated fibroblast; mTOR; renal cell carcinoma; renal fibrosis.

Publication types

  • Review

Grants and funding

This project was supported by the Research Grants Council of Hong Kong (General Research Fund 14111720, 17117923), Dr. Rita T. Liu SBS of L&T Charitable Foundation Ltd., and Bingei Family of Indo Café, Mr. Winston Leung, Mr. K.K. Chan, Ms. Siu Suet Lau, and Dr. Y.Y. Cheung and an endowment fund established at the University of Hong Kong for the Yu Professorship in Nephrology awarded to ST.