Integrin alpha6beta4 promotes expression of autotaxin/ENPP2 autocrine motility factor in breast carcinoma cells.

摘要: In advanced breast carcinomas, the alpha6beta4 integrin is associated with a migratory and invasive phenotype. our current study, we show that expression of in MDA-MB-435 carcinoma cells leads to increased autocrine motility factor autotaxin, as determined by Affymetrix gene chip, real-time quantitative RT-PCR immunoblot analyses. We further demonstrate autotaxin secretion from expressing acts enhance chemotaxis through its ability convert lysophosphatidylcholine (LPC) lysophosphatidic acid (LPA) accounts for 80% motogenic activity conditioned medium. determine alpha6beta4-dependent overexpression mediated NFAT1, but not NFAT5, use siRNAs specifically target beta4, NFAT1 NFAT5. Finally, electrophoretic mobility shift assays two consensus NFAT binding sites found promoter strongly bind cells. summary, find potentiates upregulation activation NFAT1. These observations highlight first time mechanism which transcription factors can facilitate an motile phenotype downstream signaling.