Shisa3 is associated with prolonged survival through promoting β-catenin degradation in lung cancer

Chun Chieh Chen, Hsuan Yu Chen, Kang Yi Su, Qi Sheng Hong, Bo Shiun Yan, Ching-Hsien Chen, Szu Hua Pan, Yih Leong Chang, Chia Jen Wang, Pei Fang Hung, Shinsheng Yuan, Gee Chen Chang, Jeremy J.W. Chen, Pan Chyr Yang, Ya Chien Yang, Sung Liang Yu

Research output: Contribution to journalArticle

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)433-444
Number of pages12
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume190
Issue number4
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

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Keywords

  • Metastasis
  • Non-small cell lung cancer
  • Tumor suppressor
  • WNT signaling

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Chen, C. C., Chen, H. Y., Su, K. Y., Hong, Q. S., Yan, B. S., Chen, C-H., Pan, S. H., Chang, Y. L., Wang, C. J., Hung, P. F., Yuan, S., Chang, G. C., Chen, J. J. W., Yang, P. C., Yang, Y. C., & Yu, S. L. (2014). Shisa3 is associated with prolonged survival through promoting β-catenin degradation in lung cancer. American Journal of Respiratory and Critical Care Medicine, 190(4), 433-444. https://doi.org/10.1164/rccm.201312-2256OC