Godwin Isha, Anto Nikhil Ponnoor, Bava Smitha V, Babu Mani Shankar, Jinesh Goodwin G
Saveetha Medical College, Thandalam, Chennai, Tamil Nadu, 602105, India.
Shraga Segal Department of Microbiology, Immunology and Genetics, Ben-Gurion University of the Negev, Beersheba, Israel.
Cell Death Discov. 2021 Apr 14;7(1):80. doi: 10.1038/s41420-021-00457-5.
Cellular transformation is a major event that helps cells to evade apoptosis, genomic instability checkpoints, and immune surveillance to initiate tumorigenesis and to promote progression by cancer stem cell expansion. However, the key molecular players that govern cellular transformation and ways to target cellular transformation for therapy are poorly understood to date. Here we draw key evidences from the literature on K-Ras-driven cellular transformation in the context of apoptosis to shed light on the key players that are required for cellular transformation and explain how aiming p53 could be useful to target cellular transformation. The defects in key apoptosis regulators such as p53, Bax, and Bak lead to apoptosis evasion, cellular transformation, and genomic instability to further lead to stemness, tumorigenesis, and metastasis via c-Myc-dependent transcription. Therefore enabling key apoptotic checkpoints in combination with K-Ras inhibitors will be a promising therapeutic target in cancer therapy.
细胞转化是一个重大事件，它帮助细胞逃避凋亡、基因组不稳定检查点和免疫监视，从而启动肿瘤发生，并通过癌症干细胞扩增促进肿瘤进展。然而，迄今为止，对于调控细胞转化的关键分子参与者以及针对细胞转化进行治疗的方法仍知之甚少。在这里，我们从文献中提取关于K-Ras驱动的细胞在凋亡背景下转化的关键证据，以阐明细胞转化所需的关键参与者，并解释靶向p53为何可能有助于靶向细胞转化。关键凋亡调节因子如p53、Bax和Bak的缺陷会导致凋亡逃避、细胞转化和基因组不稳定，进而通过c-Myc依赖的转录导致干性、肿瘤发生和转移。因此，使关键凋亡检查点与K-Ras抑制剂联合使用将成为癌症治疗中一个有前景的治疗靶点。
