title: Filamin C, a dysregulated protein in cancer revealed by label-free quantitative proteomic analyses of human gastric cancer cells.
abstract: Gastric cancer (GC) is the fourth and fifth most common cancer in men and women, respectively. We identified 2,750 proteins at false discovery rates of 1.3% (protein) and 0.03% (spectrum) by comparing the proteomic profiles of three GC and a normal gastric cell lines. Nine proteins were significantly dysregulated in all three GC cell lines, including filamin C, a muscle-specific filamin and a large actin-cross-linking protein. Downregulation of filamin C in GC cell lines and tissues were verified using quantitative PCR and immunohistochemistry. Data-mining using public microarray datasets shown that filamin C was significantly reduced in many human primary and metastasis cancers. Transient expression or silencing of filamin C affected the proliferation and colony formation of cancer cells. Silencing of endogenous filamin C enhanced cancer cell migration and invasion, whereas ectopic expression of filamin C had opposing effects. Silencing of filamin C increased the expression of matrix metallopeptidase 2 and improved the metastasis of prostate cancer in a zebrafish model. High filamin C associated with better prognosis of prostate cancer, leukemia and breast cancer patients. These findings establish a functional role of filamin C in human cancers and these data will be valuable for further study of its mechanisms.
authors.affiliation: Department of Medical Systems Biology of School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qiao
authors.affiliation: College of Bioscience and Biotechnology, Key Laboratory of Crop Genetics and Physiology of Jiangsu Province, Yangzhou University, Yangzhou 225009, China.
authors.forename: Shu-Jian
authors.initials: SJ
authors.lastname: Cui
authors.affiliation: Department of Medical Systems Biology of School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Lei-Lei
authors.initials: LL
authors.lastname: Xu
authors.affiliation: Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Si-Jie
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Department of Medical Systems Biology of School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of Medical Systems Biology of School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Jiang
authors.affiliation: Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Peng
authors.affiliation: Department of Chemistry, Fudan University, Shanghai 200433, China.
authors.forename: Cai-Yun
authors.initials: CY
authors.lastname: Fang
authors.affiliation: Department of Medical Systems Biology of School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.|Department of Chemistry, Fudan University, Shanghai 200433, China.
authors.forename: Peng-Yuan
authors.initials: PY
authors.lastname: Yang
authors.affiliation: Department of Medical Systems Biology of School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002853:Chromatography, Liquid; D005260:Female; D064448:Filamins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D064448:Filamins; D020543:Proteome