Transcription factors in fibroblast plasticity and CAF heterogeneity

Abstract

In recent years, research focused on the multifaceted landscape and functions of cancer-associated fibroblasts (CAFs) aimed to reveal their heterogeneity and identify commonalities across diverse tumors for more effective therapeutic targeting of pro-tumoral stromal microenvironment. However, a unified functional categorization of CAF subsets remains elusive, posing challenges for the development of targeted CAF therapies in clinical settings.The CAF phenotype arises from a complex interplay of signals within the tumor microenvironment, where transcription factors serve as central mediators of various cellular pathways. Recent advances in single-cell RNA sequencing technology have emphasized the role of transcription factors in the conversion of normal fibroblasts to distinct CAF subtypes across various cancer types.This review provides a comprehensive overview of the specific roles of transcription factor networks in shaping CAF heterogeneity, plasticity, and functionality. Beginning with their influence on fibroblast homeostasis and reprogramming during wound healing and fibrosis, it delves into the emerging insights into transcription factor regulatory networks. Understanding these mechanisms not only enables a more precise characterization of CAF subsets but also sheds light on the early regulatory processes governing CAF heterogeneity and functionality. Ultimately, this knowledge may unveil novel therapeutic targets for cancer treatment, addressing the existing challenges of stromal-targeted therapies.

Mesothelioma-Associated Fibroblasts Modulate the Response of Mesothelioma Patient-Derived Organoids to Chemotherapy via Interleukin-6

“…However, we found that the MAFs expressed SMA/A, FGF7, FAP, and PDGFR, which is partially consistent with recently published work [18]. We found heterogeneous expression of these markers, which correlates with the demonstrated heterogeneity of such cell subpopulations [34][35][36]. We were able to obtain eight mPDO cultures from twelve pleural effusions.…”

Exploring the multifaceted role of direct interaction between cancer cells and fibroblasts in cancer progression

“…Activated CAFs fall into several categories defined by their function, specific markers, and transcription factors specifying the CAFs subtypes. The extensive heterogeneity in CAFs phenotypes in diverse cancers has been comprehensively reviewed ( Biffi and Tuveson, 2021 ; Plikus et al, 2021 ; Chhabra and Weeraratna, 2023 ; Melchionna et al, 2023 ). As our understanding of CAFs heterogeneity increased, different studies identified specific subsets of CAFs in various tissues (see Table 1 ).…”