Atg7 cooperates with Pten loss to drive prostate cancer tumor growth

Urmila Santanam, Whitney Banach-Petrosky, Cory Abate-Shen, Michael M. Shen, Eileen White, Robert S. Dipaola

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

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.

Original languageEnglish
Pages (from-to)399-407
Number of pages9
JournalGenes and Development
Volume30
Issue number4
DOIs
StatePublished - Feb 15 2016

Bibliographical note

Publisher Copyright:
© 2016 Santanam et al.

Keywords

  • Autophagy
  • Castrate resistant
  • ER stress
  • Prostate cancer

ASJC Scopus subject areas

  • General Medicine

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