Schmukler Eran, Kloog Yoel, Pinkas-Kramarski Ronit
Department of Neurobiology. Tel-Aviv University, Ramat-Aviv, Israel.
Oncotarget. 2014 Feb 15;5(3):577-86. doi: 10.18632/oncotarget.1775.
Autophagy, a process of self-degradation and turnover of cellular components, plays a complex role in cancer. Evidence exists to show that autophagy may support tumor growth and cell survival, whereas it can also contribute to tumor suppression and have anti-survival characteristics in different cellular systems. Numerous studies have described the effects of various oncogenes and tumor suppressors on autophagy. The small GTPase Ras is an oncogene involved in the regulation of various cell-signaling pathways, and is mutated in 33% of human cancers. In the present review, we discuss the interplay between Ras and autophagy in relation to oncogenesis. It appears that Ras can upregulate or downregulate autophagy through several signaling pathways. In turn, autophagy can affect the tumorigenicity driven by Ras, resulting in either tumor progression or repression, depending on the cellular context. Furthermore, Ras inhibitors were shown to induce autophagy in several cancer cell lines.
自噬是细胞成分进行自我降解和更新的过程,在癌症中发挥着复杂的作用。有证据表明,自噬可能支持肿瘤生长和细胞存活,然而在不同的细胞系统中,它也可能有助于肿瘤抑制并具有抗存活特性。大量研究描述了各种癌基因和肿瘤抑制因子对自噬的影响。小GTP酶Ras是一种参与多种细胞信号通路调控的癌基因,在33%的人类癌症中发生突变。在本综述中,我们讨论了Ras与自噬在肿瘤发生过程中的相互作用。似乎Ras可以通过多种信号通路上调或下调自噬。反过来,自噬可以影响由Ras驱动的肿瘤发生能力,根据细胞环境的不同,导致肿瘤进展或抑制。此外,Ras抑制剂在几种癌细胞系中被证明可诱导自噬。