ROLE OF TRANSLOCON-ASSOCIATED PROTEIN/SIGNAL SEQUENCE RECEPTOR SUBUNITS IN HUMAN PATHOLOGICAL CONDITIONS

Abstract

The translocon-associated protein (TRAP) complex – also known as the signal sequence receptor (SSR) complex – plays a key role in protein translocation into the endoplasmic reticulum (ER), yet its contributions to cancer biology have remained underexplored. This study collectively investigates the oncogenic potential of TRAP/SSR subunits in colorectal and breast cancer. Functional knockdown of TRAPδ/SSR4 and TRAPβ/SSR2 in human colorectal cancer cell lines (HCT116, SW480, DLD-1) significantly impaired cell viability, induced cell cycle arrest at G1, S, and/or G2/M phases, and triggered apoptosis. Notably, TRAPβ/SSR2 suppression disrupted mitogen-activated protein kinase and inositol-requiring enzyme 1 alpha signaling, underscoring its role in ER stress-mediated survival pathways. In contrast, overexpression of TRAPα/SSR1 in MCF7 breast cancer cells induced viability, migration, and invasion, possibly driven by nuclear factor kappa-light-chain-enhancer of activated B cells activation and subsequent upregulation of Snail. These findings reveal distinct, subunit-specific oncogenic roles of the TRAP/SSR complex in cancer progression and highlight TRAPα/SSR1, TRAPβ/SSR2, and TRAPδ/SSR4 as promising therapeutic targets for breast and colorectal cancers.