Open AccessOverexpression of Pygopus-2 is required for canonical Wnt activation in human lung cancer
Author(s) -
Shujun Zhou,
Mei Xu,
Shaoqing Wang,
Fang Zhang,
Lei Wang,
Huaqing Wang
Publication year - 2013
Publication title -
oncology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.766
H-Index - 54
eISSN - 1792-1082
pISSN - 1792-1074
DOI - 10.3892/ol.2013.1691
Subject(s) - wnt signaling pathway , cancer research , lung cancer , small hairpin rna , biology , cancer , cell cycle , oncogene , carcinogenesis , gene knockdown , pathology , signal transduction , medicine , cell culture , microbiology and biotechnology , genetics
Lung cancer is the most common cause of cancer-related mortality worldwide. It is necessary to improve the understanding of the molecular mechanisms involved in lung cancer in order to develop more effective therapeutics for the treatment of this fatal disease. The canonical Wnt signaling pathway has been known to be important in a number of cancer types, including lung cancer. Pygopus (Pygo) is a recently identified downstream component of the Wnt signaling pathway required for β-catenin/T-cell factor (TCF)-dependent transcription. However, the role of Pygo in lung cancer remains to be elucidated. The present study showed that Pygo2 is overexpressed in human lung cancer tissue samples and cell lines. Expression levels of Pygo2 were found to correlate with cytosolic β-catenin protein levels in the samples examined. Co-immunofluorescent staining showed that Pygo2 protein accumulated in the nuclei and colocalized with nuclear β-catenin in lung cancer cell lines expressing Pygo2. To investigate the functional importance of the Pygo2 overexpression in lung cancer, short hairpin RNA (shRNA) was used to knockdown Pygo2 mRNA in lung cancer cells expressing the gene. Pygo2 shRNA was observed to inhibit cell proliferation and decrease β-catenin/TCF-dependent transcriptional activity in vitro . Furthermore, Pygo2 shRNA significantly suppressed lung cancer xenograft models in vivo (P<0.05). These results suggested that Pygo2 is a putative therapeutic target for human lung cancer and overexpression of Pygo2 may be important for aberrant Wnt activation in lung cancer.