Silencing of STRN4 suppresses the malignant characteristics of cancer cells

Cancer Sci. 2014 Dec;105(12):1526-32. doi: 10.1111/cas.12541. Epub 2014 Oct 23.

Abstract

The striatin family of proteins, comprising STRN, STRN3 and STRN4, are multidomain-containing proteins that associate with additional proteins to form a large protein complex. We previously reported that STRN4 directly associated with protein kinases, such as MINK1, TNIK and MAP4K4, which are associated with tumor suppression or tumor progression. However, it remains unclear whether STRN4 is associated with tumor progression. In this report, we examined the role that STRN4 plays in cancer malignancy. We show that depletion of STRN4 suppresses proliferation, migration, invasion and the anchorage-independent growth of cancer cells. In addition, STRN4 knockdown increases the sensitivity of pancreatic cancer cells to gemcitabine. Finally, we show that STRN4 knockdown suppresses the proliferation and metastasis of cancer cells in mice. Our results demonstrate a possible role of STRN4 in tumor progression.

Keywords: Anoikis; STRIPAK; STRN4; invasion; migration Striatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anoikis
  • Calmodulin-Binding Proteins / genetics*
  • Calmodulin-Binding Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Gemcitabine
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Knockdown Techniques
  • HCT116 Cells
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness / genetics
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / pathology*
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / pathology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology*
  • RNA, Small Interfering / metabolism

Substances

  • Calmodulin-Binding Proteins
  • Nerve Tissue Proteins
  • RNA, Small Interfering
  • STRN4 protein, human
  • STRN4 protein, mouse
  • zinedin
  • Deoxycytidine
  • Gemcitabine