HCRP-1 regulates cell migration, invasion and angiogenesis via Src/ FAK signaling in human prostate cancer

Int J Biol Sci. 2020 Jan 1;16(2):342-352. doi: 10.7150/ijbs.38112. eCollection 2020.

Abstract

Prostate cancer (PCa) is the third leading malignancy engendering mortality among men globally. The present study aimed at determining the expression of hepatocellular carcinoma-related protein-1 (HCRP-1) in PCa, to explore its potential role in prostate tumorigenesis in vitro and in vivo. We evaluated HCRP-1 protein with immunohistochemistry (IHC) technology and found HCRP-1 expression was significantly low in PCa tissues (PCTs); In addition, the decreased HCRP-1 was significantly associated with TNM (tumor node metastasis) stage, advanced histology grade and gleason score. Transwell, tube formation, Western blot and co-immunoprecipitation (Co-IP) assays were utilized to determine the role of down-regulating HCRP-1 in PCa cell migration, invasion and angiogenesis. Meanwhile, we found HCRP-1 depletion induced Src and focal adhesion kinase (FAK) phosphorylation, which could be reversed by Src inhibitor PP2 or FAK inhibitor. Furthermore, down-regulated HCRP-1 evidently induced lung metastasis of PCa cells in xenograft mode. Taken together, our study indicates HCRP-1 plays an important role in PCa metastasis. HCRP-1 may serve as a potential therapeutic target for PCa.

Keywords: HCRP-1; angiogenesis; invasion; migration; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Aged
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Cell Proliferation / genetics
  • Cell Proliferation / physiology
  • Endosomal Sorting Complexes Required for Transport / genetics
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Female
  • Focal Adhesion Protein-Tyrosine Kinases / genetics
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Immunohistochemistry
  • Male
  • Phosphorylation
  • Prostatic Neoplasms / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism

Substances

  • Endosomal Sorting Complexes Required for Transport
  • VPS37A protein, human
  • Focal Adhesion Protein-Tyrosine Kinases
  • src-Family Kinases