title: WW45, a Gli1 binding protein, negatively regulated Hedgehog signaling in lung cancer.
abstract: Over-expression of Gli1 is very common in lung cancer. However, the underlying molecular mechanism remains largely unknown. Here, using mass spectrum, we have identified WW45 as a binding partner of Gli1. WW45 interacted with Gli1, promoted its ubiquitination and inhibited the expression of its target genes. In the functional studies, WW45 inhibited the growth and migration of lung cancer cells. Knocking down the expression of WW45 promoted the growth and migration of lung cancer cells, which was rescued by down-regulation of Gli1. Moreover, over-expression of WW45 inhibited the tumorigenesis in a de novo lung cancer tumorigenesis mouse model (LKB-Ras) as well as the expression of Gli1. Also over-expression of WW45 improved the survival of these mice. In addition, the expression of WW45 was down-regulated in the clinical lung cancer samples, which was inversely correlated with the expression of Gli1. Taken together, this study demonstrated the suppressive roles of WW45 in lung cancer by inhibiting the Hedgehog/Gli1 signaling.
authors.affiliation: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Environment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Xuebing
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neuropathology, Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Xuexia
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Environment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Yaguang
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Environment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Yalong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Environment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Zu
authors.affiliation: Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yao
authors.affiliation: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Environment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.|Sichuan Lung Cancer Institute, Sichuan Lung Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000072283:A549 Cells; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D011485:Protein Binding; D015398:Signal Transduction; D000071676:Zinc Finger Protein GLI1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C415864:SAV1 protein, human; C509239:SHH protein, human; D000071676:Zinc Finger Protein GLI1
keywords: WW45; cell growth; lung cancer; migration; Hedgehog signaling