Gabarapl1 mediates androgen-regulated autophagy in prostate cancer

Tumour Biol. 2015 Nov;36(11):8727-33. doi: 10.1007/s13277-015-3542-8. Epub 2015 Jun 7.

Abstract

Autophagy plays an important role in prostate cancer development. It promotes tumor cell survival and was found to be associated with androgen pathway. In the present study, we found that GABA(A) receptor-associated protein like 1 (Gabarapl1), a ubiquitin-like modifier, participates in the regulation of autophagy. Gabarapl1 is transcriptionally regulated by androgen receptor (AR) and has a repressive role in autophagy. Androgen deprivation downregulates Gabarapl1 in an AR dependent manner, resulting in the increase of autophagy flux. Elevated Gabarapl1 also represses the proliferation of prostate cancer cells. In summary, our study provides evidence to show that Gabarapl1 is a mediator involved in androgen-regulated autophagy process.

Keywords: Androgen; Autophagy; Gabarapl1; Prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / biosynthesis*
  • Adaptor Proteins, Signal Transducing / genetics
  • Androgens / genetics
  • Androgens / metabolism*
  • Autophagy / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Microtubule-Associated Proteins / biosynthesis*
  • Microtubule-Associated Proteins / genetics
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Receptors, Androgen / biosynthesis*
  • Receptors, Androgen / genetics

Substances

  • AR protein, human
  • Adaptor Proteins, Signal Transducing
  • Androgens
  • GABARAPL1 protein, human
  • Microtubule-Associated Proteins
  • Receptors, Androgen