New insights into fibrotic signaling in renal cell carcinoma

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.

Automated high-throughput profiling of single-cell total transcriptome with scComplete-seq

“…Given the roles of snRNA on splicing and tRNA on protein translation, scComplete-seq may provide a further indication of the degree of post-transcriptional processing that would shape the cell phenotype. Additionally, we showed that scComplete-seq could detect eRNA expression, which generally correlates with enhancer activation and can serve as a direct marker of active enhancers 38,39 . GO analysis of the putative genes targeted by these enhancers showed enrichment in biological processes consistent with these cell types while further analysis of these eRNA revealed distinct transcription factor motifs that could explain the mechanisms of gene regulation.…”

Combination of Anti-Angiogenics and Immunotherapies in Renal Cell Carcinoma Show Their Limits: Targeting Fibrosis to Break through the Glass Ceiling?

“…Intratumoural fibrosis is a histologic manifestation of fibrotic tumour stroma, and its presence in ccRCC has been associated with poor prognosis and cancer aggressiveness. Intratumoural fibrosis is positively correlated with the histological grade of ccRCC and intratumoural inflammation [90,91]. The interaction between cancer cells and fibrotic stroma is intricate and reciprocal, involving dysregulations from multiple biological processes.…”