PDF(Pubmed)
Abstract：
Cancer testis antigens (CTAs) are a collection of proteins whose expression is normally restricted to the gamete but abnormally activated in a wide variety of tumors. The CTA, Testis-specific serine kinase 6 (TSSK6), is essential for male fertility in mice. The 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 relapse-free survival. Depletion of TSSK6 from colorectal cancer cells attenuates anchorage-independent growth, invasion, and growth in vivo. Conversely, overexpression of TSSK6 enhances anchorage independence and invasion in vitro as well as in vivo tumor growth. Notably, ectopic expression of TSSK6 in semi-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 that TSSK6 exhibits oncogenic activity when abnormally expressed in colorectal cancer cells. Thus, TSSK6 is a previously unrecognized intervention target for therapy, which could exhibit an exceptionally broad therapeutic window.
摘要：
癌症睾丸抗原（CTAs）是蛋白质的集合，其表达通常限于配子，但在多种肿瘤中异常激活。CTA,睾丸特异性丝氨酸激酶6(TSSK6),对小鼠的雄性生育能力至关重要。TSSK6与癌症的功能相关性，如果有的话,以前没有被调查过。在这里，我们发现TSSK6在结直肠癌中经常异常表达，TSSK6表达升高的患者无复发生存率降低。结直肠癌细胞中TSSK6的耗竭减弱了锚定非依赖性生长，体内的侵袭和生长。相反，TSSK6的过表达增强了体外和体内肿瘤生长的锚定独立性和侵袭性。值得注意的是,TSSK6在半转化的人结肠上皮细胞中的异位表达足以赋予锚定独立性并增强侵袭性。在体细胞中，TSSK6与paxillin和张力蛋白阳性灶在细胞外周共同定位并增强其形成，表明在粘着斑形成中的作用。重要的是,TSSK6激酶活性是诱导这些致瘤行为所必需的。我们的发现确定TSSK6在结直肠癌细胞中异常表达时表现出致癌活性。因此，TSSK6是以前未被认可的治疗干预靶点，这可能表现出非常广阔的治疗窗口。
