Expression of Serum Response Factor in Gastric Carcinoma and Its Molecular Mechanisms Involved in the Regulation of the Invasion and Migration of SGC-7901 Cells

Abstract

Serum response factor (SRF) is a transcription factor of the MADS box family. To date, DNA binding sites for SRF [serum response elements (SREs)] have been found in the promoters of approximately 50 different genes known to be involved in the regulation cell proliferation, differentiation, and apoptosis. Recent studies have indicated that SRF plays a role in the development of some tumors, including hepatocellular, thyroid, esophageal, and lung carcinomas. However, expression of SRF and its roles in gastric carcinoma are unclear. We found SRF to be highly expressed in human gastric carcinoma as well as ectopic or reduced expression for E-cadherin and β-catenin. Blockage of SRF expression was found to inhibit proliferation, invasion, and migration. We also found that an inhibitor (Y-27632) of Rho-associated coiled kinase (ROCK1), a regulator of actin cytoskeleton that regulates cell adhesion, migration, and motility, suppressed SRF expression as well. These results demonstrate that SRF is involved in the aggressive behavior of gastric carcinoma cells. We also found that the inhibition of ROCK1 by Y-27632 can inhibit the invasion and migration of gastric cells done at least, in part, by attenuating SRF expression.

Migrastatics—Anti-metastatic and Anti-invasion Drugs: Promises and Challenges

“…It was shown to decrease the invasive activity of rat hepatoma MM1 cells and their dissemination in the peritoneal cavity [89]; inhibit the metastatic growth of human prostatic cancer PC3 cells in immune-compromised mice [90]; decrease intrahepatic metastasis of primary human hepatoma LI7 cells [91]; decrease the bombesin-stimulated invasiveness of Isreco 1 human colon carcinoma cells [92]; and decrease the invasiveness of human MDA-MB-231 breast carcinoma cells [93], A375m2 and WM266.4 human melanoma cells, LS174T human colon carcinoma cells [19], LPA-induced invasiveness of human hepatoma SMMC-7721 cells [94], human anaplastic thyroid cancer ARO cells [95], shear stress-induced invasiveness of human esophageal cancer OC-1 cells [96] and VMRC-LCD human non-small-cell lung cancer cells [97]. In addition, Y-27632 significantly inhibited intrahepatic metastasis orthotropic implantation of CBO140C12 HCC tumor fragments into mice liver [98], and decreased the invasiveness of B16F1 mouse melanoma cells; UvMel 1.3, UvMel 1.5, and UvMel 270 human uveal melanoma cells [99]; PRL-1-expressing A549 human lung carcinoma cells [100]; AMFR-induced motility of esophageal squamous carcinoma cells [101]; LPA-induced invasiveness of human ovarian cancer CAOV-3 and PA-1 cells [102]; SGC-7901 human gastric carcinoma cells [103]; human colorectal carcinoma SW620 cells [104]; U87MG human glioma cells [105]; human hepatocellular carcinoma cells [106]; metastases of HT29 human colorectal carcinoma cells in an orthotropic mouse model of liver metastasis [107]; Y79 human retinoblastoma cells [108]; and Tca8113 and CAL-27 human tongue squamous cell carcinoma cells [109].…”

Targeting the cytoskeleton against metastatic dissemination

“…Further, it impaired the invasive abilities of B16F1 mouse melanoma cells; UvMel 1.3, UvMel 1.5, and UvMel 270 human uveal melanoma cells [490]; human anaplastic thyroid cancer ARO cells [491], U87MG human glioma cells [492]; Y79 human retinoblastoma cells [493]; and Tca8113 and CAL-27 human tongue squamous cell carcinoma cells [494]. Y-27632 anti-invasive effects were also visible on SGC-7901 human gastric carcinoma cells [495]; human colorectal carcinoma SW620 cells [496] and human hepatocellular carcinoma cells [497]. Finally, Y-27632 has been shown to reduce the metastatic growth of human prostate cancer PC3 cells in immune-compromised mice [498]; to significantly decrease intrahepatic metastasis orthotropic implantation of CBO140C12 HCC tumour fragments into mice liver [499], and to impair the metastatic dissemination of HT29 human colorectal carcinoma cells in an orthotropic mouse model of liver metastasis [500].…”

Serum response factor: positive and negative regulation of an epithelial gene expression network in the destrin mutant cornea

“…These studies highlight the essential role of SRF in the control of gene expression within and among tissues throughout the body of the organism. Improper or misregulated expression of SRF has been implicated in numerous cancers (25,38,47), and SRF activity has been found to be modulated by actin dynamics by several in vitro studies (1,20,21). This study uses a unique model to identify how F-actin-driven increased SRF transcriptional activity leads to increased proliferation, recruitment of inflammatory molecules, and angiogenesis in vivo.…”