The Role of Atg5 Gene in Tumorigenesis Under Autophagy Deficiency Conditions

    Hsiao‐Sheng Liu, Yinping Wang, Pei‐Wen Lin, Man‐Ling Chu, Sheng‐Hui Lan, Shan‐Ying Wu, Ying‐Ray Lee, Hong Chang
    TLDR Atg5 can promote tumors when autophagy is deficient but suppresses them under normal conditions.
    The study examines the Atg5 gene's role in tumorigenesis under autophagy deficiency, using mouse embryonic fibroblast cell lines with knockouts of autophagy-related genes. It reveals that Atg5 has a dual role, acting as a tumor suppressor under normal autophagy but promoting tumorigenesis when autophagy is impaired. Overexpression of Atg5 in autophagy-deficient cells increased proliferation and migration, suggesting a tumor-promoting role. In vivo, Atg5 overexpression transiently promoted tumor formation, which regressed upon autophagy restoration. The Wnt5a/JNK/β-catenin signaling pathway is implicated in Atg5-mediated tumorigenesis under deficient conditions, highlighting autophagy's critical role in cancer development.
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