Characterising the Cell-Surface Proteins in ARID1A-deficient Gastric Cancer

Abstract

Chromatin remodellers play a pivotal role in controlling gene expression thereby playing prominent roles in tumour progression. AT-Rich Interacting Domain 1A (ARID1A) is a non-catalytic subunit of the SWI/SNF chromatin remodelling complex that is frequently mutated in various cancers. Gastric cancer is one of the leading causes of cancer mortality across the world and harbours ARID1A mutation in about 30% of cases. Despite being implicated with various synthetic lethal targets, there remains to be limited clinical efficacy associated with ARID1A deficiency in tumour cells. The cellular surface proteome, often referred to as the ‘surfaceome,’ acts as a vital interface between afflicted cells and their immediate microenvironment. Within the context of cancer, this domain not only defines the biology of tumours but also represents a valuable reservoir of potential biomarkers targets for therapy. Here, we try to characterize the surfaceome in non-isogenic ARID1A-deficient and ARID1A Wild-Type (WT) gastric cancer cell lines to compare and identify specific protein targets that can negatively influence the tumour microenvironment (TME) or act as potential drug targets. This was followed by an in-silico transcriptome analysis from TCGA to validate our findings as well as to gain probable mechanistic insights into the function of ARID1A-deficient tumour cells. Interestingly, we report the enrichment of proteins that primarily regulate migration, metastasis and proteins that lead to an immunosuppressive TME. In concert with these findings, we also found a significant enrichment of mitochondrial genes that regulate oxidative phosphorylation which several other studies have found in SWI/SNF-deficient tumours.