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http://dx.doi.org/10.14348/molcells.2020.0075

Characterization of TNNC1 as a Novel Tumor Suppressor of Lung Adenocarcinoma  

Kim, Suyeon (Department of Life Science, Ewha Womans University)
Kim, Jaewon (Department of Life Science, Ewha Womans University)
Jung, Yeonjoo (Department of Life Science, Ewha Womans University)
Jun, Yukyung (Department of Life Science, Ewha Womans University)
Jung, Yeonhwa (Ewha Research Center for Systems Biology, Ewha Womans University)
Lee, Hee-Young (Ewha Research Center for Systems Biology, Ewha Womans University)
Keum, Juhee (Ewha Research Center for Systems Biology, Ewha Womans University)
Park, Byung Jo (Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine)
Lee, Jinseon (Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine)
Kim, Jhingook (Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine)
Lee, Sanghyuk (Department of Life Science, Ewha Womans University)
Kim, Jaesang (Department of Life Science, Ewha Womans University)
Publication Information
Molecules and Cells / v.43, no.7, 2020 , pp. 619-631 More about this Journal
Abstract
In this study, we describe a novel function of TNNC1 (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 TNNC1 was strongly down-regulated in cancer tissues compared to matched normal lung tissues, and down-regulation of TNNC1 was shown to be strongly correlated with increased mortality among LUAD patients. Interestingly, TNNC1 expression was enhanced by suppression of KRAS, and ectopic expression of TNNC1 in turn inhibited KRASG12D-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 TNNC1. In addition, ectopic expression of TNNC1 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 TNNC1 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 TNNC1 led to significant enhancement of invasiveness in vitro. Collectively, our data indicate that TNNC1 has a novel function as a tumor suppressor and is targeted for down-regulation by KRAS pathway during the carcinogenesis of LUAD.
Keywords
invasion; KRAS; lung adenocarcinoma; TNNC1; tumor suppressor;
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