An antiproliferative gene FLNA regulates migration and invasion of gastric carcinoma cell in vitro and its clinical significance

This study aimed to analyze the expression and clinical significance of filamin A (FLNA) in gastric carcinoma and the biological effect in its cell line by FLNA overexpression. Immunohistochemistry and western blot were used to analyze FLNA protein expression in 47 cases of gastric cancer and 47 cases of normal tissues to study the relationship between FLNA expression and clinical factors. FLNA lentiviral vector and empty vector were respectively transfected into gastric cancer SGC-7901 cell line. Reverse transcription–polymerase chain reaction (RT–PCR) and western blot were used to detect the mRNA level and protein of FLNA. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and migration and invasion assays were also conducted to determine the influence of the upregulated expression of FLNA that might be found on SGC-7901 cell biological effect. Immunohistochemistry: The level of FLNA protein expression was found to be significantly lower in gastric cancer tissue than normal tissues (P < 0.05). Western blot: The relative amount of FLNA protein in gastric cancer tissue was found to be significantly lower than in normal tissues (P < 0.05). The level of FLNA protein expression was not correlated with gender, age, and tumor invasion (P > 0.05), but it was correlated with lymph node metastasis, clinic stage, and histological grade (P < 0.05). Loss of FLNA expression correlated significantly with poor overall survival time by Kaplan–Meier analysis (P < 0.05). The result of biological function showed that SGC-7901 cell transfected FLNA had a lower survival fraction, significant decrease in migration and invasion, and lower matrix metallopeptidase 9 (MMP-9) protein expression compared with SGC-7901 cell untransfected FLNA (P < 0.05). FLNA expression decreased in gastric cancer and correlated significantly with lymph node metastasis, clinic stage, histological grade, and poor overall survival, suggesting that FLNA may play important roles as a negative regulator to gastric cancer SGC-7901 cell by promoting degradation of MMP-9.

[1]  J. Hartwig,et al.  Filamins as integrators of cell mechanics and signalling , 2001, Nature Reviews Molecular Cell Biology.

[2]  Charles E. Schwartz,et al.  Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans , 2003, Nature Genetics.

[3]  Fumihiko Nakamura,et al.  Structural basis of filamin A functions , 2007, The Journal of cell biology.

[4]  J. R. Kelley,et al.  Gastric cancer epidemiology and risk factors. , 2003, Journal of clinical epidemiology.

[5]  J. Borén,et al.  Filamins in cardiovascular development. , 2007, Trends in cardiovascular medicine.

[6]  E. J. Simon,et al.  Filamin A Mutant Lacking Actin-Binding Domain Restores Mu Opioid Receptor Regulation in Melanoma Cells , 2008, Neurochemical Research.

[7]  Baocun Sun,et al.  BMP-6 promotes E-cadherin expression through repressing δEF1 in breast cancer cells , 2007, BMC Cancer.

[8]  L. Bourguignon,et al.  Heregulin-mediated ErbB2-ERK Signaling Activates Hyaluronan Synthases Leading to CD44-dependent Ovarian Tumor Cell Growth and Migration* , 2007, Journal of Biological Chemistry.

[9]  Christopher A. Walsh,et al.  Filamin A and Filamin B are co-expressed within neurons during periods of neuronal migration and can physically interact. , 2002, Human molecular genetics.

[10]  X. Zhang,et al.  Matrine inhibits matrix metalloproteinase-9 expression and invasion of human hepatocellular carcinoma cells , 2011, Journal of Asian natural products research.

[11]  Yan Li,et al.  FLNA and PGK1 are Two Potential Markers for Progression in Hepatocellular Carcinoma , 2011, Cellular Physiology and Biochemistry.

[12]  A. Chinnaiyan,et al.  Nuclear versus Cytoplasmic Localization of Filamin A in Prostate Cancer: Immunohistochemical Correlation with Metastases , 2009, Clinical Cancer Research.

[13]  M. Crow,et al.  Interaction of Filamin A with the Insulin Receptor Alters Insulin-dependent Activation of the Mitogen-activated Protein Kinase Pathway* , 2003, Journal of Biological Chemistry.

[14]  D. Roder,et al.  The epidemiology of gastric cancer , 2002, Gastric Cancer.

[15]  Yingwei Xue,et al.  Expression of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in gastric adenocarcinoma , 2011, Journal of surgical oncology.

[16]  Gilbert S Omenn,et al.  Differential protein expression profiling by iTRAQ-2DLC-MS/MS of lung cancer cells undergoing epithelial-mesenchymal transition reveals a migratory/invasive phenotype. , 2006, Journal of proteome research.

[17]  P. Morin,et al.  Filamin A-mediated Down-regulation of the Exchange Factor Ras-GRF1 Correlates with Decreased Matrix Metalloproteinase-9 Expression in Human Melanoma Cells* , 2007, Journal of Biological Chemistry.

[18]  C. Walsh,et al.  The many faces of filamin: A versatile molecular scaffold for cell motility and signalling , 2004, Nature Cell Biology.