Ectopic Otoconin 90 Expression in Triple Negative Breast Cancer Cell Lines is Associated with Metastasis Functions

Triple negative breast cancer (TNBC) is an aggressive tumor with propensity to metastasize and poor treatment options. Improving treatment options would be impactful; thus, finding a tumor-specific cell surface protein with metastasis promoting functions that could be knocked out was the goal of this study. The Otoconin 90 gene (OC90), frequently amplified in tumors on chromosome 8q24.22, was identified as a potential therapeutic candidate. Normally OC90 is expressed in the cochlea with no known function in other normal tissues. In silico analysis of The Cancer Genome Atlas (TCGA) multi-tumor RNAseq cohorts revealed that OC90 is expressed in many tumor types at high prevalence and genomic amplification is associated with the elevated mRNA expression. In vitro assays in TNBC cell lines revealed OC90 expression with control over cell viability, apoptosis and invasion. RNA-seq analysis of OC90-siRNA knockdown and OC90-overexpression in BT20, BT549, HCC38 cell lines identified co-expressed transcripts, HMGA2, POLE2 and TRIB3. Altered expression of HMGA2, POLE2 and TRIB3 was predictive of survival among members of the Metabric breast cancer cohort. Thus, OC90 represents a potential therapeutic target whose knockdown could improve the treatment of TNBC.