Filamin C, a dysregulated protein in cancer revealed by label-free quantitative proteomic analyses of human gastric cancer cells
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Jie Qiao1,*, Shu-Jian Cui3,*, Lei-Lei Xu1, Si-Jie Chen4, Jun Yao1, Ying-Hua Jiang1, Gang Peng4, Cai-Yun Fang2, Peng-Yuan Yang1,2,*, Feng Liu1,*
1Department of Medical Systems Biology of School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
2Department of Chemistry, Fudan University, Shanghai 200433, China
3College of Bioscience and Biotechnology, Key Laboratory of Crop Genetics and Physiology of Jiangsu Province, Yangzhou University, Yangzhou 225009, China.
4Institutes of Brain Science, Fudan University, Shanghai 200032, China
*These authors contributed equally to this work
Feng Liu, e-mail: firstname.lastname@example.org
Peng-Yuan Yang, e-mail: email@example.com
Keywords: Gastric cancer, Proteomics, Filamin C, Metastasis, Tumor suppressor
Received: July 03, 2014 Accepted: October 26, 2014 Published: November 28, 2014
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.
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