Nischarin negatively impacts ShcD-mediated tumor cell migration

Abstract

ShcD was previously found to promote cell motility in melanoma cells. Screening of a yeast two hybrid mouse embryo cDNA library identified Nischarin, a negative regulator to cell motility, as an interacting partner to the ShcD-CH2 domain. Therefore, we aimed to investigate the interaction between Nischarin and ShcD in mammalian cells and to determine their functional impact on cell migration. The Nischarin/ShcD interaction was confirmed by transfection and co-immunoprecipitation assays using full-length constructs in HEK293, MCF7 and MM253 cell lines. Deletion of the first 93 amino acids of ShcD abrogated the interaction indicating the importance of these residues for Nischarin binding. Co-expression of Nischarin and ShcD demonstrated an inhibitory effect on the levels of phospho-ERK and phospho-LIMK. In support of this, Nischarin was found to block the migratory activities of ShcD. A brief in silico analysis of publicly available breast cancer patient data was performed to elucidate the effect of Nischarin/ShcD co-expression on the patients overall survival. Patients with high expression of both proteins had better survival than those with only ShcD overexpression. Our results reveal that the novel protein Nischarin is an interacting partner to ShcD. In addition, we report that the tumour suppressive abilities of Nischarin can overcome ShcD-mediated cell migration when both proteins are concomitantly expressed. *This abstract was presented in the National Cancer Research Institute (NCRI)-2019