Shisa3 is associated with prolonged survival through promoting β-catenin degradation in lung cancer
Journal
American Journal of Respiratory and Critical Care Medicine
Journal Volume
190
Journal Issue
4
Pages
433-444
Date Issued
2014
Author(s)
Chen C.-C.
Chen H.-Y.
Hong Q.-S.
Chen C.-H.
Wang C.-J.
Hung P.-F.
Yuan S.
Chang G.-C.
Chen J.J.W.
Abstract
Rationale: Despite advances in treatment and prognosis of non-small cell lung cancer (NSCLC), patient outcomes are still unsatisfactory. Objectives: To reduce the morbidity and mortality of patients with NSCLC, a more comprehensive understanding of mechanisms involved in cancer progression is urgently needed. Methods: By 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 Results: We 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. Conclusions: Our results reveal that Shisa3 acts as a tumor suppressor by acceleration of β-catenin degradation and provide new insight for cancer prognosis and therapy. Copyright ? 2014 by the American Thoracic Society.
SDGs
Other Subjects
beta catenin; shisa3 protein; tumor suppressor protein; unclassified drug; beta catenin; membrane protein; Shisa protein, mouse; anchorage independent growth; animal experiment; animal model; apoptosis; Article; cancer growth; cancer inhibition; cancer patient; cancer survival; cell invasion; cell migration; cell proliferation; controlled study; correlational study; epithelial mesenchymal transition; gene expression profiling; human; human cell; in vitro study; lung carcinogenesis; lung function; microarray analysis; morbidity; mortality; mouse; non small cell lung cancer; nonhuman; outcome assessment; overall survival; priority journal; progression free survival; protein degradation; tail vein; tumor growth; aged; animal; article; cell motion; cell survival; disease model; genetics; lung non small cell cancer; lung tumor; metabolism; metastasis; methodology; Non-small cell lung cancer; polymerase chain reaction; SCID mouse; signal transduction; Taiwan; tumor cell culture; tumor suppressor; Western blotting; WNT signaling; metastasis; non-small cell lung cancer; tumor suppressor; WNT signaling; Aged; Animals; Apoptosis; beta Catenin; Blotting, Western; Carcinoma, Non-Small-Cell Lung; Cell Movement; Cell Proliferation; Cell Survival; Disease Models, Animal; Humans; Lung Neoplasms; Membrane Proteins; Mice; Mice, SCID; Microarray Analysis; Polymerase Chain Reaction; Signal Transduction; Taiwan; Tumor Cells, Cultured
Publisher
American Thoracic Society
Type
journal article