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A distinctive form of autophagy induced by oncogenic RAS. | LitMetric

RAS mutations enhance macroautophagy/autophagy in tumor cells, crucial for their growth and survival, making autophagy a promising therapeutic target for RAS-mutant cancers. However, the distinction between RAS-induced autophagy and physiological autophagy is not well understood. We recently identified a unique form of autophagy, RAS-induced non-canonical autophagy via ATG8ylation (RINCAA), which differs from starvation-induced autophagy. RINCAA is regulated by different sets of autophagic factors and forms structures distinct from the double-membrane autophagosome known as RAS-induced multivesicular/multilaminar bodies of ATG8ylation (RIMMBA). A key feature of RINCAA is the phosphorylation of PI4KB by ULK1, and inhibiting this phosphorylation shows superior effects compared to general autophagy inhibitors. This work suggests a potential for specifically targeting autophagy in RAS-driven cancers as a therapeutic strategy.

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http://dx.doi.org/10.1080/15548627.2025.2468917DOI Listing

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