Journal
CANCER CELL
Volume 25, Issue 5, Pages 666-681Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2014.03.010
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Funding
- National Natural Science Foundation of China [81330037, 81372240, 81071680, 81071700, 81171936, 81171937, 31171251]
- National Natural Science Foundation of Shanghai [12ZR1437200]
- SMMU [2011QN02]
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The role of TGF-beta-induced epithelial-mesenchymal transition (EMT) in cancer cell dissemination is well established, but the involvement of lncRNAs in TGF-beta signaling is still unknown. In this study, we observed that the lncRNA-activated by TGF-beta (lncRNA-ATB) was upregulated in hepatocellular carcinoma (HCC) metastases and associated with poor prognosis. lncRNA-ATB upregulated ZEB1 and ZEB2 by competitively binding the miR-200 family and then induced EMT and invasion. In addition, lncRNA-ATB promoted organ colonization of disseminated tumor cells by binding IL-11 mRNA, autocrine induction of IL-11, and triggering STAT3 signaling. Globally, lncRNA-ATB promotes the invasion-metastasis cascade. Thus, these findings suggest that lncRNA-ATB, a mediator of TGF-beta signaling, could predispose HCC patients to metastases and may serve as a potential target for antimetastatic therapies.
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