The Cancer Testis Antigen Testis Specific Serine Kinase 6 (TSSK6) is abnormally expressed in colorectal cancer and is essential for oncogenic behaviors

Abstract

AbstractCancer testis antigens (CTAs) are a collection of proteins whose expression is normally restricted to the testis, but abnormally activated in a wide variety of tumors. The CTA, Testis specific serine kinase 6 (TSSK6), is essential for male fertility in mice. Functional relevance of TSSK6 to cancer, if any, has not previously been investigated. Here we find that TSSK6 is frequently anomalously expressed in colorectal cancer and patients with elevated TSSK6 expression have reduced regression free survival. Depletion of TSSK6 from colorectal cancer cells attenuates anchorage independent growth, invasion and growth in vivo. Conversely, overexpression of TSSK6 promotes neoplastic behaviors in vitro and enhances in vivo tumor growth. Notably, ectopic expression of TSSK6 in non-transformed human colonic epithelial cells is sufficient to confer anchorage independence and enhance invasion. In somatic cells, TSSK6 co-localizes with and enhances the formation of paxillin and tensin positive foci at the cell periphery, suggesting a function in focal adhesion formation. Importantly, TSSK6 kinase activity is essential to induce these tumorigenic behaviors. Our findings establish TSSK6 as a previously unknown oncogenic kinase. The requirement of TSSK6 for tumor cell growth presents it as an intervention target for therapy, which could exhibit an exceptionally broad therapeutic window.