Kinase D-interacting substrate of 220kDa is overexpressed in gastric cancer and associated with local invasion

Background: Kinase D-interacting substrate of 220kDa (Kidins220), also known as ankyrin repeat-rich membrane spanning protein (ARMS) is a transmembrane scaffold protein. It has been indicated in various malignancies including melanoma, glioma, neuroblastoma, prostate cancer, pancreatic cancer, and ovarian cancer. Materials and Methods: In the current study, Kidins220 expression was determined at transcript and protein levels. Kidins220 knockdown cell model was established to identify its role in cellular functions including cell cycle, proliferation, and invasion. The relevant cell signalling was analysed by protein array and TCGA gastric cancer cohort. Results: Kidins220 transcript was significantly increased in gastric tumors in comparison with adjacent normal tissues. More advanced tumors (TNM3 and TNM4) exhibited higher protein levels of Kidins220 compared with early-stage tumors (TNM1 and TNM2). Increased expression of Kidins220 in gastric cancer was associated with poorer overall survival. Loss of Kidins220 promoted cell invasion and adhesion of gastric cancer and correlated to EMT and MMP signalling. Knockdown of Kidins220 allowed more cells to enter into G2/M phase in gastric cancer and attribute to cell proliferation with corresponding alteration in cell cycle regulators. Conclusion: Our study identified an increased expression of Kidins220 in gastric cancer, which is associated with disease progression and poor prognosis. The disease progression in gastric cancer can be promoted by the loss of Kidins220 via EMT, MMP and cell cycle signalling