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- Title
TGF-β Modulated Pathways in Colorectal Cancer: New Potential Therapeutic Opportunities.
- Authors
Fasano, Morena; Pirozzi, Mario; Miceli, Chiara Carmen; Cocule, Mariateresa; Caraglia, Michele; Boccellino, Mariarosaria; Vitale, Pasquale; De Falco, Vincenzo; Farese, Stefano; Zotta, Alessia; Ciardiello, Fortunato; Addeo, Raffaele
- Abstract
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.
- Subjects
COLORECTAL cancer; SMAD proteins; EXTRACELLULAR matrix; DIAGNOSIS; CELL nuclei
- Publication
International Journal of Molecular Sciences, 2024, Vol 25, Issue 13, p7400
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms25137400