Atg7 cooperates with Pten loss to drive prostate cancer tumor growth
Autor: | Urmila Santanam, Whitney Banach-Petrosky, Michael M. Shen, Cory Abate-Shen, Eileen White, Robert S. DiPaola |
---|---|
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Male Carcinogenesis medicine.disease_cause Autophagy-Related Protein 7 Animals Genetically Modified 03 medical and health sciences Prostate cancer Mice Prostate Genetics medicine Autophagy PTEN Animals biology PTEN Phosphohydrolase Prostatic Neoplasms medicine.disease Endoplasmic Reticulum Stress Disease Models Animal Prostatic Neoplasms Castration-Resistant 030104 developmental biology medicine.anatomical_structure Tumor progression biology.protein Unfolded protein response Cancer research Microtubule-Associated Proteins Gene Deletion Developmental Biology Signal Transduction Research Paper |
Zdroj: | Genesdevelopment. 30(4) |
ISSN: | 1549-5477 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |