Baba Abdul Basit, Rah Bilal, Bhat Gh Rasool, Mushtaq Ifra, Parveen Sabra, Hassan Rukhsana, Hameed Zargar Mahrukh, Afroze Dil
Advanced Centre for Human Genetics, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, India.
Front Pharmacol. 2022 Feb 28;13:791272. doi: 10.3389/fphar.2022.791272. eCollection 2022.
A ubiquitously expressed cytokine, transforming growth factor-beta (TGF-β) plays a significant role in various ongoing cellular mechanisms. The gain or loss-of-function of TGF-β and its downstream mediators could lead to a plethora of diseases includes tumorigenesis. Specifically, at the early onset of malignancy TGF-β act as tumour suppressor and plays a key role in clearing malignant cells by reducing the cellular proliferation and differentiation thus triggers the process of apoptosis. Subsequently, TGF-β at an advanced stage of malignancy promotes tumorigenesis by augmenting cellular transformation, epithelial-mesenchymal-transition invasion, and metastasis. Besides playing the dual roles, depending upon the stage of malignancy, TGF-β also regulates cell fate through immune and stroma components. This oscillatory role of TGF-β to fight against cancer or act as a traitor to collaborate and crosstalk with other tumorigenic signaling pathways and its betrayal within the cell depends upon the cellular context. Therefore, the current review highlights and understands the dual role of TGF-β under different cellular conditions and its crosstalk with other signaling pathways in modulating cell fate.
转化生长因子-β（TGF-β）是一种广泛表达的细胞因子，在各种正在进行的细胞机制中发挥着重要作用。TGF-β及其下游介质的功能获得或丧失可能导致包括肿瘤发生在内的多种疾病。具体而言，在恶性肿瘤发生的早期，TGF-β作为肿瘤抑制因子，通过减少细胞增殖和分化来清除恶性细胞，从而触发细胞凋亡过程，发挥关键作用。随后，在恶性肿瘤的晚期，TGF-β通过增强细胞转化、上皮-间质转化、侵袭和转移来促进肿瘤发生。除了发挥双重作用外，根据恶性肿瘤的阶段，TGF-β还通过免疫和基质成分调节细胞命运。TGF-β对抗癌症或充当叛徒与其他致癌信号通路协作和相互作用的这种振荡作用及其在细胞内的背叛取决于细胞环境。因此，本综述着重探讨并理解TGF-β在不同细胞条件下的双重作用及其与其他信号通路在调节细胞命运方面的相互作用。
