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.