Abstract
BackgroundCoronin 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.MethodsThis 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.ResultsHistopathological 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.ConclusionsWe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1645-7) contains supplementary material, which is available to authorized users.
Highlights
Coronin proteins are known as regulators of actin-based cellular processes, and some of them are associated with the malignant progression of human cancer
We demonstrate that the expression level of CRN5 is associated with the malignant progression of colon carcinoma, and that CRN5 over-expression led to elevated tumour cell migration velocity as well as altered MAPK14 and Protein arginine N-methyltransferase 5 (PRMT5) signalling pathways
CRN5 expression is up-regulated in colon carcinoma Expression of CRN5 in human colon tumours was investigated by histopathological analyses using our mouse monoclonal antibody K77-578-1
Summary
Coronin proteins are known as regulators of actin-based cellular processes, and some of them are associated with the malignant progression of human cancer. Coronin proteins belong to the superfamily of eukaryoticspecific WD40-repeat domain proteins [5]. They play important roles in the regulation of F-actin dynamics in numerous cellular processes including the migration and invasion of tumour cells [6]. Based on the observations that CRN5 interacts with the cofilin-activating phosphatase Slingshot-1 L and knock-down of CRN5 increases the amount of phospho-cofilin, CRN5 has been implicated in the regulation of the focal adhesion turnover rate [11]. In absence of SUMOylated LXRs CRN5 binds to oligomeric nuclear actin enabling NCoR clearance and de-repression of Toll-like receptor-induced inflammatory response genes in macrophages [13]
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