西亞試劑：Down-Regulation of Autophagy-Related Protein 5 (ATG5) Contr

Down-Regulation of Autophagy-Related Protein 5 (ATG5) Contributes to the Pathogenesis of Early-Stage Cutaneous Melanoma

He Liu1, Zhaoyue He1, Thomas von Rütte1, Shida Yousefi1, Robert E. Hunger2 and Hans-Uwe Simon1,*

The role of autophagy in cancer is controversial: Both tumor-suppressing and tumor-promoting functions have been reported. We show that a key regulator of autophagy, autophagy-related protein 5 (ATG5), is often down-regulated in primary melanomas compared to benign nevi, leading to a reduction of basal autophagy as evidenced by a reduced expression of LC3. A follow-up of 158 primary melanoma patients showed that patients with low levels of ATG5 in their tumors had a reduced progression-free survival. In an in vitro model of melanoma tumorigenesis, where the BRAF oncogene was transduced into normal melanocytes, we observed that lowering ATG5 expression promoted proliferation by precluding oncogene-induced senescence. Hence, it appears that down-regulation of ATG5 contributes to tumorigenesis in early-stage cutaneous melanoma, and the expression of ATG5 and LC3 correlates with melanoma diagnosis and prognosis.

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