The transformation of cancer-associated fibroblasts: Current perspectives on the role of TGF-β in CAF mediated tumor progression and therapeutic resistance

• Published in: Cancer letters 2021-11, Vol.520, p.222-232
• Main Authors: Chandra Jena, Bikash, Sarkar, Siddik, Rout, Lipsa, Mandal, Mahitosh
• Format: Article
• Language: English
• Subjects: Amino acids; Biomarkers; Breast cancer; Cancer; Cancer-Associated Fibroblasts - drug effects; Cancer-Associated Fibroblasts - metabolism; Cancer-Associated Fibroblasts - pathology; Carcinogenesis - genetics; Cell differentiation; Cell Differentiation - drug effects; Cell migration; Cell Proliferation - drug effects; Chemoresistance; Clinical trials; Cytokines; Drug resistance; Drug Resistance, Neoplasm - genetics; Exosomes; Extracellular matrix; Fibroblasts; Growth factors; Humans; Kinases; Metabolites; Metastasis; Morphology; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - pathology; Paracrine signalling; Proteins; Signal Transduction; Smad protein; Smad Proteins - genetics; Stem cell; Stem cells; Stroma; TGF-β activation; Transforming Growth Factor beta - genetics; Transforming growth factor-b; Tumor cells; Tumor Microenvironment - drug effects; Tumor-stroma crosstalk; Tumors; Wound healing
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2021.08.002

Over the last few years, the Transforming growth factor- β (TGF-β) has been significantly considered as an effective and ubiquitous mediator of cell growth. The cytokine, TGF-β is being increasingly recognized as the most potent inducer of cancer cell initiation, differentiation, migration as well as progression through both the SMAD-dependent and independent pathways. There is growing evidence that supports the role of secretory cytokine TGF-β as a crucial mediator of tumor-stroma crosstalk. Contextually, the CAFs are the prominent component of tumor stroma that helps in tumor progression and onset of chemoresistance. The interplay between the CAFs and the tumor cells through the paracrine signals is facilitated by cytokine TGF-β to induce the malignant progression. Here in this review, we have dissected the most recent advancements in understanding the mechanisms of TGF-β induced CAF activation, their multiple origins, and most importantly their role in conferring chemoresistance. Considering the pivotal role of TGF-β in tumor perogression and associated stemness, it is one the proven clinical targets We have also included the clinical trials going on, targeting the TGF-β and CAFs crosstalk with the tumor cells. Ultimately, we have underscored some of the outstanding issues that must be deciphered with utmost importance to unravel the successful strategies of anti-cancer therapies. [Display omitted] •CAFs are the prominent component of the tumor microenvironment modulating the tumorigenic features.•TGF-β has been significantly considered as an effective and ubiquitous mediator of cell growth.•TGF-β has a dichotomous role in both tumor-promoting and tumor retarding.•TGF-β in CAFs significantly contributes to cancer drug resistance.•Targeting the TGF-β signaling can have a therapeutic benefit in successful cancer management.