Abstract 3432: HLJ1 serves as an inhibitor of epithelial-mesenchymal transition by inactivating β-catenin signaling

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL HLJ1 (DnaJ-like heat shock protein), also known as DNAJB4, was classified as a tumor suppressor gene. The expression of HLJ1 inversely associates with invasive ability and can predict the clinical outcomes of non-small-cell lung cancer (NSCLC) patients. However, the role of HLJ1 in suppressing cancer metastasis is still unclear. Here, we identified HLJ1 as a novel inhibitor of epithelial-mesenchymal transition (EMT). Our functional assays in vitro and in vivo demonstrated that Knock-down of HLJ1 promotes invasion capabilities of lung cancer cells and causes liver macrometastasis; meanwhile, the crucial domain of HLJ1 in suppression of cancer invasion was also confirmed. We found that the HLJ1-overexpressing cells maintain the well-organized cell adhesion and polarity. Inversely, an increase in actin polymerization and the formation of actin stress fibers were observed in the HLJ1-silencing cells. HLJ1 down-regulates the transcriptional activities of slug promoter and facilitates E-cadherin transcription, leading to the inhibition of epithelial to mesenchymal transition. Further, we identified the Wnt/β-catenin signalling pathway in which HLJ1 involved by cDNA microarray and pathway analysis. The subcellular distribution of β-catenin is predominant in the nucleus and the tyrosine-phosphorylated levels of β-catenin are up-regulated in the HLJ1-silenced clones. Finally, we showed a decreased accumulation of β-catenin and an enhanced degradation of β-catenin in absence of HLJ1 expression. Taken together, our study reveals that HLJ1 has anti-metastatic activity by repressing β-catenin signaling and provides a molecular model for the development of new anticancer agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3432. doi:1538-7445.AM2012-3432