The effect of S100A6 on nuclear translocation of CacyBP/SIP in colon cancer cells

PLoS One. 2018 Mar 13;13(3):e0192208. doi: 10.1371/journal.pone.0192208. eCollection 2018.

Abstract

Background: Calcyclin Binding Protein/(Siah-1 interacting protein) (CacyBP/SIP) acts as an oncogene in colorectal cancer. The nuclear accumulation of CacyBP/SIP has been linked to the proliferation of cancer cells. It has been reported that intracellular Ca2+ induces the nuclear translocation of CacyBP/SIP. However, the molecular mechanism of CacyBP/SIP nuclear translocation has yet to be elucidated. The purpose of this study was to test whether the Ca2+-dependent binding partner S100 protein is involved in CacyBP/SIP nuclear translocation in colon cancer SW480 cells.

Methods: The subcellular localization of endogenous CacyBP/SIP was observed following the stimulation of ionomycin or BAPTA/AM by immunofluorescence staining in SW480 cells. S100A6 small interfering RNAs (siRNA) were transfected into SW480 cells. Immunoprecipitation assays detected whether S100 protein is relevant to the nuclear translocation of CacyBP/SIP in response to changes in [Ca2+]i.

Results: We observed that endogenous CacyBP/SIP is translocated from the cytosol to the nucleus following the elevation of [Ca2+]i by ionomycin in SW480 cells. Co-immunoprecipitation experiments showed that the interaction between S100A6 and CacyBP/SIP was increased simultaneously with elevated Ca2+. Knockdown of S100A6 abolished the Ca2+ effect on the subcellular translocation of CacyBP/SIP.

Conclusion: Thus, we demonstrated that S100A6 is required for the Ca2+-dependent nuclear translocation of CacyBP/SIP in colon cancer SW480 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Calcium / metabolism
  • Calcium Ionophores / pharmacology
  • Calcium-Binding Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Nucleus / metabolism*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ionomycin / pharmacology
  • RNA Interference
  • S100 Calcium Binding Protein A6 / genetics
  • S100 Calcium Binding Protein A6 / metabolism*

Substances

  • CACYBP protein, human
  • Calcium Ionophores
  • Calcium-Binding Proteins
  • S100 Calcium Binding Protein A6
  • Ionomycin
  • Calcium

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 81072040 to HHZ); The Technology Foundation for Selected Overseas Chinese Scholar, Ministry of Personnel of China and National Key Technologies R&D Program (No. 2015BAI13B09 to HHZ). The corresponding author played an important role in the study design, data collection and analysis, decision to publish, and preparation of the manuscript.