Actin protrusion at the cell periphery is central to the formation of invadopodia during tumor cell migration and invasion. Although RUFY3 (RUN and FYVE domain containing 3)/SINGAR1 (single axon-related1)/RIPX (Rap2 interacting protein X) has an important role in neuronal development, its pathophysiologic role and relevance to cancer are still largely unknown. The purpose of this study was to elucidate the molecular mechanisms by which RUFY3 involves in gastric cancer cell migration and invasion. Here, our data show that overexpression of RUFY3 leads to the formation of F-actin-enriched protrusive structures at the cell periphery and induces gastric cancer cell migration. Furthermore, P21-activated kinase-1 (PAK1) interacts with RUFY3, and promotes RUFY3 expression and RUFY3-induced gastric cancer cell migration; inhibition of PAK1 attenuates RUFY3-induced SGC-7901 cell migration and invasion. Importantly, we found that the inhibitory effect of cell migration and invasion is significantly enhanced by knockdown of both PAK1 and RUFY3 compared with knockdown of RUFY3 alone or PAK1 alone. Strikingly, we found significant upregulation of RUFY3 in gastric cancer samples with invasive carcinoma at pathologic TNM III and TNM IV stages, compared with their non-tumor counterparts. Moreover, an obvious positive correlation was observed between the protein expression of RUFY3 and PAK1 in 40 pairs of gastric cancer samples. Therefore, these findings provide important evidence that PAK1 can positively regulate RUFY3 expression, which contribute to the metastatic potential of gastric cancer cells, maybe blocking PAK1-RUFY3 signaling would become a potential metastasis therapeutic strategy for gastric cancer.
Pubmed ID: 25766321 RIS Download
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NIH initiative project to provide full-length open reading frame (FL-ORF) clones for human, mouse, and rat genes, cow. MGC cDNA clones were obtained by screening of cDNA libraries, by transcript-specific RT-PCR cloning, and by DNA synthesis of cDNA inserts. All MGC sequences are deposited in GenBank and clones can be purchased from distributors of IMAGE consortium. With conclusion of MGC project in March 2009, GenBank records of MGC sequences will be frozen, without further updates. Since definition of what constitutes full-length coding region for some of genes and transcripts for which they have MGC clones will likely change in future, users planning to order MGC clones will need to monitor for these changes. Users can make use of genome browsers and gene-specific databases, such as the UCSC Genome browser, NCBI's Map Viewer, and Entrez Gene, to view relevant regions of genome (browsers) or gene-related information (Entrez Gene).
View all literature mentionsCell line COS-7 is a Transformed cell line with a species of origin Chlorocebus aethiops (Green monkey)
View all literature mentionsCell line SGC-7901 is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsCell line BGC-823 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SGC-7901 is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
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