title: Overexpression of Pygopus-2 is required for canonical Wnt activation in human lung cancer.
abstract: 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 activityin vitro. Furthermore, Pygo2 shRNA significantly suppressed lung cancer xenograft modelsin 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.
authors.affiliation: Department of Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China.
authors.forename: Shi-Yong
authors.initials: SY
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Tianjin Chest Hospital, Tianjin 300051, P.R. China.
authors.forename: Mei-Lin
authors.initials: ML
authors.lastname: Xu
authors.affiliation: Longyao Hospital, Longyao County, Xingtai, Hebei 055350, P.R. China.
authors.forename: Shao-Qing
authors.initials: SQ
authors.lastname: Wang
authors.affiliation: Tsinghua University Graduate School at Shenzhen, Division of Life and Health Sciences, Shenzhen, Guangdong 518055, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China.
authors.forename: Hua-Qing
authors.initials: HQ
authors.lastname: Wang
keywords: Pygopus-2; RNAi; Wnt activation; inhibition; lung cancer