%0 Journal Article
%T TGF-β Modulated Pathways in Colorectal Cancer: New Potential Therapeutic Opportunities.
%A Fasano M
%A Pirozzi M
%A Miceli CC
%A Cocule M
%A Caraglia M
%A Boccellino M
%A Vitale P
%A De Falco V
%A Farese S
%A Zotta A
%A Ciardiello F
%A Addeo R
%J Int J Mol Sci
%V 25
%N 13
%D 2024 Jul 5
%M 39000507
%F 6.208
%R 10.3390/ijms25137400
%X Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, with 20% of patients presenting with metastatic disease at diagnosis. TGF-β signaling plays a crucial role in various cellular processes, including growth, differentiation, apoptosis, epithelial-mesenchymal transition (EMT), regulation of the extracellular matrix, angiogenesis, and immune responses. TGF-β signals through SMAD proteins, which are intracellular molecules that transmit TGF-β signals from the cell membrane to the nucleus. Alterations in the TGF-β pathway and mutations in SMAD proteins are common in metastatic CRC (mCRC), making them critical factors in CRC tumorigenesis. This review first analyzes normal TGF-β signaling and then investigates its role in CRC pathogenesis, highlighting the mechanisms through which TGF-β influences metastasis development. TGF-β promotes neoangiogenesis via VEGF overexpression, pericyte differentiation, and other mechanisms. Additionally, TGF-β affects various elements of the tumor microenvironment, including T cells, fibroblasts, and macrophages, promoting immunosuppression and metastasis. Given its strategic role in multiple processes, we explored different strategies to target TGF-β in mCRC patients, aiming to identify new therapeutic options.