PDF(Pubmed)
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.
摘要：
结直肠癌（CRC）是全球第三大最常见的癌症，20%的患者在诊断时出现转移性疾病。TGF-β信号在各种细胞过程中起着至关重要的作用，包括增长,分化,凋亡，上皮-间质转化（EMT），细胞外基质的调节，血管生成,和免疫反应。TGF-β信号通过SMAD蛋白，它们是将TGF-β信号从细胞膜传递到细胞核的细胞内分子。TGF-β途径的改变和SMAD蛋白的突变在转移性CRC（mCRC）中很常见，使它们成为CRC肿瘤发生的关键因素。这篇综述首先分析了正常的TGF-β信号，然后研究了其在CRC发病机制中的作用。强调TGF-β影响转移发展的机制。TGF-β通过VEGF过表达促进血管新生,周细胞分化,和其他机制。此外,TGF-β影响肿瘤微环境的各种元素，包括T细胞,成纤维细胞,和巨噬细胞，促进免疫抑制和转移。鉴于其在多个流程中的战略作用，我们探索了mCRC患者靶向TGF-β的不同策略，旨在确定新的治疗方案。
