Coronin 2A (CRN5) expression is associated with colorectal adenoma-adenocarcinoma sequence and oncogenic signalling

BMC Cancer. 2015 Sep 15;15:638. doi: 10.1186/s12885-015-1645-7.

Abstract

Background: Coronin proteins are known as regulators of actin-based cellular processes, and some of them are associated with the malignant progression of human cancer. Here, we show that expression of coronin 2A is up-regulated in human colon carcinoma.

Methods: This study included 26 human colon tumour specimens and 9 normal controls. Expression and localisation of coronin 2A was studied by immunohistochemistry, immunofluorescence imaging, cell fractionation, and immunoblotting. Functional roles of coronin 2A were analysed by over-expression and knock-down of the protein. Protein interactions were studied by co-immunoprecipitation and pull-down experiments, mass spectrometry analyses, and in vitro kinase and methylation assays.

Results: Histopathological investigation revealed that the expression of coronin 2A in colon tumour cells is up-regulated during the adenoma-adenocarcinoma progression. At the subcellular level, coronin 2A localised to multiple compartments, i.e. F-actin stress fibres, the front of lamellipodia, focal adhesions, and the nuclei. Over-expression of coronin 2A led to a reduction of F-actin stress fibres and elevated cell migration velocity. We identified two novel direct coronin 2A interaction partners. The interaction of coronin 2A with MAPK14 (mitogen activated protein kinase 14 or MAP kinase p38α) led to phosphorylation of coronin 2A and also to activation of the MAPK14 pathway. Moreover, coronin 2A interacted with PRMT5 (protein arginine N-methyltransferase 5), which modulates the sensitivity of tumour cells to TRAIL-induced cell death.

Conclusions: We show that increased expression of coronin 2A is associated with the malignant phenotype of human colon carcinoma. Moreover, we linked coronin 2A to MAPK14 and PRMT5 signalling pathways involved in tumour progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adenoma / genetics*
  • Adenoma / metabolism*
  • Adenoma / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism
  • Mitogen-Activated Protein Kinase 14 / metabolism
  • Phosphorylation
  • Protein Transport
  • Protein-Arginine N-Methyltransferases / metabolism
  • Pseudopodia / metabolism
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism
  • Signal Transduction*
  • Stress Fibers / metabolism
  • Substrate Specificity

Substances

  • Microfilament Proteins
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • coronin proteins
  • PRMT5 protein, human
  • Protein-Arginine N-Methyltransferases
  • Mitogen-Activated Protein Kinase 14