2619

GAS1

growth arrest-specific 1;GAS1;growth arrest-specific 1

GAS-1|Growth arrest-specific gene-1|growth arrest-specific protein 1

9q21.3-q22

protein-coding

Growth arrest-specific gene 1 had been associated with cell-cycle arrest, proliferation, and apoptosis. The aim of this study was to investigate the correlations between clinicopathologic factors and survival time and growth arrest-specific gene 1 expression in patients with stage II and III colorectal cancer (CRC). Quantitative real-time polymerase chain reaction was performed in 64 fresh CRC tissues to examine growth arrest-specific gene 1 mRNA expression. Six metastasis-derived and primary-derived cell lines were subjected to quantitative real-time polymerase chain reaction and Western blotting for further examination of both mRNA and protein concentrations. Growth arrest-specific gene 1 protein was immunostained in 118 paraffin-embedded specimens. Growth arrest-specific gene 1 expression was down-regulated both in tissues with recurrence and in metastasis-derived cell lines. expression was unrelated to sex, age, tumor grade, or lymphovascular or perineural invasion. However, it was positively related to disease-free survival time (P < .05). Furthermore, lower growth arrest-specific gene 1 expression indicated a poorer survival rate (P < .05; log-rank test). Multivariate analysis also showed weak growth arrest-specific gene 1 protein expression to be an independent adverse prognosticator (P < .05). Taken together, our results support the idea that growth arrest-specific gene 1 contributes to predicting metastasis or recurrence in stage II and III CRC.

metastasis suppressor genes inhibit one or more steps required for metastasis without affecting primary tumor formation. Due to the complexity of the metastatic process, the development of experimental approaches for identifying genes involved in metastasis prevention has been challenging. Here we describe a genome-wide RNAi screening strategy to identify candidate metastasis suppressor genes. Following expression in weakly metastatic B16-F0 mouse melanoma cells, shRNAs were selected based upon enhanced satellite colony formation in a three-dimensional cell culture system and confirmed in a mouse experimental metastasis assay. Using this approach we discovered 22 genes whose knockdown increased metastasis without affecting primary tumor growth. We focused on one of these genes, Gas1 (Growth arrest-specific 1), because we found that it was substantially down-regulated in highly metastatic B16-F10 melanoma cells, which contributed to the high metastatic potential of this mouse cell line. We further demonstrated that Gas1 has all the expected properties of a melanoma tumor suppressor including: suppression of metastasis in a spontaneous metastasis assay, promotion of apoptosis following dissemination of cells to secondary sites, and frequent down-regulation in human melanoma metastasis-derived cell lines and metastatic tumor samples. Thus, we developed a genome-wide shRNA screening strategy that enables the discovery of new metastasis suppressor genes.