title: Wwox suppresses breast cancer cell growth through modulation of the hedgehog-GLI1 signaling pathway.
abstract: Wwox is a tumor suppressor that is frequently deleted or altered in several cancer types, including breast cancer. Previous studies have shown that ectopic expression of Wwox inhibits proliferation of breast cancer cells. However, the underlying mechanism remains unclear. To better understand the molecular mechanisms of Wwox function, we investigated novel partners of this protein. Utilizing the coimmunoprecipitation assay, we observed a physical association between Wwox and the Gli1 zinc-finger transcription factor involved in the hedgehog pathway. Our results further demonstrated that Wwox expression triggered redistribution of nuclear Gli1 to the cytoplasm. Additionally, ectopic expression of Wwox reduced Gli1 expression in vitro. Furthermore, Gli1 Blocks Wwox-induced breast cancer cell growth inhibition. These findings suggest a functional crosstalk between Wwox and hedgehog-GLI1 signaling pathway in tumorigenesis.
authors.affiliation: Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai, PR China.
authors.forename: Anwen
authors.initials: A
authors.lastname: Xiong
authors.affiliation: Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai, PR China; Department of Oncology, NO. 401 hospital of PLA, Qingdao, Shandong, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai, PR China.
authors.forename: Mingzhen
authors.initials: M
authors.lastname: Ying
authors.affiliation: Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai, PR China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Hua
authors.affiliation: Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai, PR China. Electronic address: yajiewang@live.com.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Wang
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000074584:WW Domain-Containing Oxidoreductase; D000071676:Zinc Finger Protein GLI1
chemical_list: C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000071676:Zinc Finger Protein GLI1; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human
keywords: Breast cancer; Gli1; Hedgehog; Wwox