Abstract

BackgroundAutophagy has paradoxical and complex functions in cancer development, and autophagy-related genes (ATG) are key regulators in autophagy. Until now, more than 30 different ATG proteins have been identified in yeast, and their mammalian counterparts also have been reported. Although the roles of a few ATG proteins in cancer have been characterized, the role of ATG10 is almost completely unknown.Methodology/Principal FindingsTo investigate the clinicopathological role of ATG10 in colorectal cancer, we analyzed ATG10 expression in colorectal cancer tissues and cell lines. Protein expression analysis showed that ATG10 is highly increased in colorectal cancer (tissue - 18/37 cases, 48%; cell line –8/12 cell lines, 66%). Immunohistochemical analysis with clinicopathological features indicated a strong association of the up-regulation of ATG10 with tumor lymph node metastasis (p = 0.005) and invasion (p<0.001). Moreover, both 5-year disease free survival and overall survival rates of patients bearing tumors that did not express ATG10 were significantly higher than those of patients bearing ATG10-expressing tumors (p = 0.012).Conclusion/SignificanceIncreased expression of ATG10 in colorectal cancer is associated with lymphovascular invasion and lymph node metastasis indicating that ATG10 may be a potential prognostic maker in colorectal cancer.

Highlights

  • The ubiquitin/26S proteasome system is one of the major pathways regulating protein turnover in cells

  • Our findings show that increased ATG10 expression is strongly associated with lymph node metastasis and lymphovascular invasion in colorectal cancer

  • These results indicate that ATG10 is upregulated in colorectal cancer

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Summary

Introduction

The ubiquitin/26S proteasome system is one of the major pathways regulating protein turnover in cells. Autophagosome formation is regulated by a family of evolutionally conserved autophagy-related gene (ATG) proteins [2,3]. Ubiquitin (Ub) conjugation is a well-coordinated event that requires E1, E2, and E3 enzymes [4]. Activated ATG8 or ATG12 is transferred to the E2-like conjugation enzymes, ATG3 and ATG10. The ATG8phosphatidylethanolamine (PE) and ATG12-ATG5 conjugates are formed. The ATG12-ATG5 conjugate forms a complex with. Autophagy has paradoxical and complex functions in cancer development, and autophagy-related genes (ATG) are key regulators in autophagy. The roles of a few ATG proteins in cancer have been characterized, the role of ATG10 is almost completely unknown

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