A curated census of autophagy-modulating proteins and small molecules

Abstract

Autophagy, a programmed process in which cell contents are delivered to lysosomes for degradation, appears to have both tumor-suppressive and tumor-promoting functions; both stimulation and inhibition of autophagy have been reported to induce cancer cell death, and particular genes and proteins have been associated both positively and negatively with autophagy. To provide a basis for incisive analysis of those complexities and ambiguities and to guide development of new autophagy-targeted treatments for cancer, we have compiled a comprehensive, curated inventory of autophagy modulators by integrating information from published siRNA screens, multiple pathway analysis algorithms, and extensive, manually curated text-mining of the literature. The resulting inventory includes 739 proteins and 385 chemicals (including drugs, small molecules, and metabolites). Because autophagy is still at an early stage of investigation, we provide extensive analysis of our sources of information and their complex relationships with each other. We conclude with a discussion of novel strategies that could potentially be used to target autophagy for cancer therapy.

Keywords: :

• autophagy
• cancer
• high-throughput screening
• L-asparaginase
• natural language processing
• pathway analysis
• RNAi
• siRNA
• text-mining

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

We thank Shelley Herbrich, Kevin Coombes, and Ganiraju Manyam (UT MD Anderson Cancer Center) for assistance in dealing with gene names and synonyms and all of the researchers whose publications formed the basis for this census.

JNW’s and PLL’s work was supported in part by US. National Cancer Institute (NCI) grant numbers CA143883 (The Cancer Genome Atlas MD Anderson Genome Data Analysis Center) and CA083639 (University of Texas MD Anderson SPORE in Ovarian Cancer), the Cancer Prevention Research Institute of Texas (CPRIT) grant number RP130397, and also by the Chapman Foundation and the Michael and Susan Dell Foundation (honoring Lorraine Dell). GBM’s work was supported in part by Komen Foundation grants KG 081694 and FAS0703849, and by the Ovarian Cancer Research Fund. SC’s work was supported by an Odyssey Program Fellowship, by the Theodore N. Law Endowment for Scientific Achievement at the University of Texas MD Anderson Cancer Center, and by NCI Breast SPORE Career Developmental Project award CA116199.