DEPDC1 promotes cell proliferation and tumor growth via activation of E2F signaling in prostate cancer

Biochem Biophys Res Commun. 2017 Aug 26;490(3):707-712. doi: 10.1016/j.bbrc.2017.06.105. Epub 2017 Jun 19.

Abstract

DEP domain containing 1 (DEPDC1) is recently reported to be overexpressed in several types of human cancer; however the role of DEPDC1 in prostate cancer remains to be investigated. Herein, we identified that the DEPDC1 mRNA and protein expression levels were dramatically increased in prostate cancer tissues and cell lines. Overexpression of DEPDC1 promoted, but depletion of DEPDC1 inhibited cell proliferation by regulating the G1-S phase cell cycle transition. Importantly, we found that DEPDC1 was essential for the tumor growth and formation of bone metastases of prostate cancer cells in vivo. Finally, we demonstrated that DEPDC1 interacted with E2F1 and increased its transcriptional activity, leading to hyper-activation of E2F signaling in prostate cancer cells. Our findings reveal an oncogenic role of DEPDC1 in prostate cancer progression via activation of E2F signaling, and suggest DEPDC1 might be a potential therapeutic target against the disease.

Keywords: Bone metastasis; Cell cycle; DEPDC1; E2F; Prostate cancer; Tumorigencity.

MeSH terms

  • Animals
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Bone Neoplasms / secondary
  • Bone and Bones / metabolism
  • Bone and Bones / pathology
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation
  • E2F Transcription Factors / metabolism*
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Prostate / metabolism
  • Prostate / pathology*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Signal Transduction*
  • Up-Regulation

Substances

  • DEPDC1 protein, human
  • E2F Transcription Factors
  • GTPase-Activating Proteins
  • Neoplasm Proteins