title: Atg7 cooperates with Pten loss to drive prostate cancer tumor growth.
abstract: Understanding new therapeutic paradigms for both castrate-sensitive and more aggressive castrate-resistant prostate cancer is essential to improve clinical outcomes. As a critically important cellular process, autophagy promotes stress tolerance by recycling intracellular components to sustain metabolism important for tumor survival. To assess the importance of autophagy in prostate cancer, we generated a new autochthonous genetically engineered mouse model (GEMM) with inducible prostate-specific deficiency in the Pten tumor suppressor and autophagy-related-7 (Atg7) genes. Atg7 deficiency produced an autophagy-deficient phenotype and delayed Pten-deficient prostate tumor progression in both castrate-naïve and castrate-resistant cancers. Atg7-deficient tumors display evidence of endoplasmic reticulum (ER) stress, suggesting that autophagy may promote prostate tumorigenesis through management of protein homeostasis. Taken together, these data support the importance of autophagy for both castrate-naïve and castrate-resistant growth in a newly developed GEMM, suggesting a new paradigm and model to study approaches to inhibit autophagy in combination with known and new therapies for advanced prostate cancer.
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA;
authors.forename: Urmila
authors.initials: U
authors.lastname: Santanam
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA;
authors.forename: Whitney
authors.initials: W
authors.lastname: Banach-Petrosky
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, New York 10032, USA; Department of Urology, Columbia University Medical Center, New York, New York 10032, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York 10032, USA; Department of Systems Biology, Columbia University Medical Center, New York, New York 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York 10032, USA;
authors.forename: Cory
authors.initials: C
authors.lastname: Abate-Shen
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, New York 10032, USA; Department of Urology, Columbia University Medical Center, New York, New York 10032, USA; Department of Systems Biology, Columbia University Medical Center, New York, New York 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York 10032, USA; Department of Genetics and Development, Columbia University Medical Center, New York, New York 10032, USA;
authors.forename: Michael M
authors.initials: MM
authors.lastname: Shen
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA; Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA.
authors.forename: Eileen
authors.initials: E
authors.lastname: White
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA;
authors.forename: Robert S
authors.initials: RS
authors.lastname: DiPaola
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001343:Autophagy / Q000235:genetics; D000071193:Autophagy-Related Protein 7; D063646:Carcinogenesis / Q000235:genetics* / Q000473:pathology*; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D017353:Gene Deletion; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics / Q000503:physiopathology; D015398:Signal Transduction / Q000235:genetics
chemical_list: C502661:Atg7 protein, mouse; D008869:Microtubule-Associated Proteins; D051059:PTEN Phosphohydrolase; D000071193:Autophagy-Related Protein 7
keywords: ER stress; autophagy; castrate resistant; prostate cancer