• Pan-Chyr Yang, Sung-Liang Yu, Shin-Sheng Yuan, Kang-Yi Su, Qi-Sheng Hong, Bo-Shiun Yan, Szu-Hua Pan, Pei-Fang Hung, Gee-Chen Chang, and Ya-Chien Yang.
• 1 Department of Clinical Laboratory Sciences and Medical Biotechnology.
• Am. J. Respir. Crit. Care Med.. 2014 Aug 15;190(4):433-44.

RationaleDespite advances in treatment and prognosis of non-small cell lung cancer (NSCLC), patient outcomes are still unsatisfactory.ObjectivesTo reduce the morbidity and mortality of patients with NSCLC, a more comprehensive understanding of mechanisms involved in cancer progression is urgently needed.MethodsBy comparison of gene expression profiles in the cell line pair with differential invasion ability, CL1-0 and CL1-5, we found that Shisa3 was highly expressed in the low invasive cells. The effect of Shisa3 on invasion, migration, proliferation, apoptosis, epithelial-mesenchymal transition, and anchorage-independent growth activities in vitro and on tumor growth and metastasis in mice models were examined. The underlying mechanism of Shisa3 was explored by microarray and pathway analysis. Finally, the correlation of Shisa3 expression and clinical outcome was also calculated.Measurements And Main ResultsWe identified Shisa3 as a novel tumor suppressor, which induces β-catenin degradation resulting in suppression of tumorigenesis and invasion in vitro. Shisa3 decreased the tumor growth in mice with subcutaneous implantation and reduced the number of metastatic nodules in mice with tail vein injection and orthotopic implantation. Shisa3 performs the tumor suppression activity through WNT signaling predicted by microarray analysis. Our data found that Shisa3 accelerates β-catenin degradation and was positively associated with overall survival and progression-free survival of NSCLC.ConclusionsOur results reveal that Shisa3 acts as a tumor suppressor by acceleration of β-catenin degradation and provide new insight for cancer prognosis and therapy.

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