Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan Key Laboratory of Medical Bioactive Molecular Developmental and Translational Research, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, Guangdong, 523808, China.
Institute of Laboratory Medicine, School of Medical Technology, Guangdong Medical University, Dongguan, Guangdong, 523808, China.
Int J Med Sci. 2024 May 13;21(7):1307-1320. doi: 10.7150/ijms.96274. eCollection 2024.
Transforming growth factor-β (TGF-β) is strongly associated with the cell adhesion signaling pathway in cell differentiation, migration, etc. Mechanistically, TGF-β is secreted in an inactive form and localizes to the extracellular matrix (ECM) via the latent TGF-β binding protein (LTBP). However, it is the release of mature TGF-β that is essential for the activation of the TGF-β signaling pathway. This progress requires specific integrins (one of the main groups of cell adhesion molecules (CAMs)) to recognize and activate the dormant TGF-β. In addition, TGF-β regulates cell adhesion ability through modulating CAMs expression. The aberrant activation of the TGF-β signaling pathway, caused by abnormal expression of key regulatory molecules (such as Smad proteins, certain transcription factors, and non-coding RNAs), promotes tumor invasive and metastasis ability via epithelial-mesenchymal transition (EMT) during the late stages of tumorigenesis. In this paper, we summarize the crosstalk between TGF-β and cell adhesion signaling pathway in cancer and its underlying molecular mechanisms.
转化生长因子-β(TGF-β)与细胞黏附信号通路在细胞分化、迁移等方面密切相关。从机制上讲,TGF-β以无活性形式分泌,并通过潜伏 TGF-β 结合蛋白(LTBP)定位于细胞外基质(ECM)。然而,成熟 TGF-β 的释放对于 TGF-β 信号通路的激活是必不可少的。这一进展需要特定的整合素(细胞黏附分子(CAMs)的主要群体之一)识别和激活休眠的 TGF-β。此外,TGF-β 通过调节 CAMs 的表达来调节细胞黏附能力。在肿瘤发生的晚期,关键调节分子(如 Smad 蛋白、某些转录因子和非编码 RNA)的异常表达导致 TGF-β 信号通路的异常激活,通过上皮-间充质转化(EMT)促进肿瘤的侵袭和转移能力。本文总结了 TGF-β 与癌症中细胞黏附信号通路的相互作用及其潜在的分子机制。