Characterization of as a Novel Tumor Suppressor of Lung Adenocarcinoma.

In this study, we describe a novel function of (Troponin C1, Slow Skeletal and Cardiac Type), a component of actin-bound troponin, as a tumor suppressor of lung adenocarcinoma (LUAD). First, the expression of was strongly down-regulated in cancer tissues compared to matched normal lung tissues, and down-regulation of was shown to be strongly correlated with increased mortality among LUAD patients. Interestingly, expression was enhanced by suppression of , and ectopic expression of in turn inhibited -mediated anchorage independent growth of NIH3T3 cells. Consistently, activation of KRAS pathway in LUAD patients was shown to be strongly correlated with down-regulation of . In addition, ectopic expression of inhibited colony formation of multiple LUAD cell lines and induced DNA damage, cell cycle arrest and ultimately apoptosis. We further examined potential correlations between expression levels of and various clinical parameters and found that low-level expression is significantly associated with invasiveness of the tumor. Indeed, RNA interference-mediated down-regulation of led to significant enhancement of invasiveness . Collectively, our data indicate that has a novel function as a tumor suppressor and is targeted for down-regulation by KRAS pathway during the carcinogenesis of LUAD.