Legorreta Cancer Center, The Warren Alpert Medical School, Brown University, Providence, RI 02912, USA; Department of Pathology and Lab Medicine, The Warren Alpert Medical School, Brown University, Providence, RI 02912, USA.
Legorreta Cancer Center, The Warren Alpert Medical School, Brown University, Providence, RI 02912, USA; Department of Pathology and Lab Medicine, The Warren Alpert Medical School, Brown University, Providence, RI 02912, USA.
Semin Cancer Biol. 2023 Oct;95:120-139. doi: 10.1016/j.semcancer.2023.08.002. Epub 2023 Aug 11.
Cancer cells adapt to varying stress conditions to survive through plasticity. Stem cells exhibit a high degree of plasticity, allowing them to generate more stem cells or differentiate them into specialized cell types to contribute to tissue development, growth, and repair. Cancer cells can also exhibit plasticity and acquire properties that enhance their survival. TGF-β is an unrivaled growth factor exploited by cancer cells to gain plasticity. TGF-β-mediated signaling enables carcinoma cells to alter their epithelial and mesenchymal properties through epithelial-mesenchymal plasticity (EMP). However, TGF-β is a multifunctional cytokine; thus, the signaling by TGF-β can be detrimental or beneficial to cancer cells depending on the cellular context. Those cells that overcome the anti-tumor effect of TGF-β can induce epithelial-mesenchymal transition (EMT) to gain EMP benefits. EMP allows cancer cells to alter their cell properties and the tumor immune microenvironment (TIME), facilitating their survival. Due to the significant roles of TGF-β and EMP in carcinoma progression, it is essential to understand how TGF-β enables EMP and how cancer cells exploit this plasticity. This understanding will guide the development of effective TGF-β-targeting therapies that eliminate cancer cell plasticity.
癌细胞通过可塑性来适应不同的应激条件以存活。干细胞表现出高度的可塑性，使它们能够产生更多的干细胞或分化为专门的细胞类型，以促进组织发育、生长和修复。癌细胞也可以表现出可塑性，并获得增强其存活的特性。TGF-β 是癌细胞利用的无与伦比的生长因子，以获得可塑性。TGF-β 介导的信号转导使癌细胞能够通过上皮间质可塑性 (EMP) 改变其上皮和间充质特性。然而，TGF-β 是一种多功能细胞因子；因此，TGF-β 的信号转导对癌细胞可能有害也可能有益，这取决于细胞环境。那些克服 TGF-β 抗肿瘤作用的细胞可以诱导上皮间质转化 (EMT) 以获得 EMP 的益处。EMP 使癌细胞能够改变其细胞特性和肿瘤免疫微环境 (TIME)，从而促进其存活。由于 TGF-β 和 EMP 在癌进展中具有重要作用，因此了解 TGF-β 如何使 EMP 成为可能以及癌细胞如何利用这种可塑性至关重要。这种理解将指导开发有效的 TGF-β 靶向治疗方法，以消除癌细胞的可塑性。
