Ras and autophagy in cancer development and therapy.
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Eran Schmukler1, Yoel Kloog1 and Ronit Pinkas-Kramarski1
1 Department of Neurobiology. Tel-Aviv University, Ramat-Aviv, Israel.
Pinkas-Kramarski Ronit, email:
Keywords: Autophagy, Ras, cancer, oncogene
Received: January 6, 2014 Accepted: February 13, 2014 Published: February 13, 2014
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.
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