TGF-ß Modulated Pathways in Colorectal Cancer: New Potential Therapeutic Opportunities.
Int J Mol Sci
; 25(13)2024 Jul 05.
Article
en En
| MEDLINE
| ID: mdl-39000507
ABSTRACT
Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, with 20% of patients presenting with metastatic disease at diagnosis. TGF-ß 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-ß signals through SMAD proteins, which are intracellular molecules that transmit TGF-ß signals from the cell membrane to the nucleus. Alterations in the TGF-ß 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-ß signaling and then investigates its role in CRC pathogenesis, highlighting the mechanisms through which TGF-ß influences metastasis development. TGF-ß promotes neoangiogenesis via VEGF overexpression, pericyte differentiation, and other mechanisms. Additionally, TGF-ß 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-ß in mCRC patients, aiming to identify new therapeutic options.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
/
Transducción de Señal
/
Factor de Crecimiento Transformador beta
/
Microambiente Tumoral
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Mol Sci
Año:
2024
Tipo del documento:
Article
País de afiliación:
Italia