Journal
NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-020-18929-0
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Funding
- National Natural Science Foundation of China [81820108025, 81621004, 81672296, 81922050, 81772473, 81802274, 81972170]
- Science and Technology Program of Guangzhou City [201803010039]
- Guangdong MEPP Fund [GDOE[2019]A21]
- Natural Science Foundation of Guangdong Province [2019A1515011174]
- Fundamental Research Funds for the Central Universities [19ykpy162]
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Despite the importance of AKT overactivation in tumor progression, results from clinical trials of various AKT inhibitors remain suboptimal, suggesting that AKT-driven tumor metastasis needs to be further understood. Herein, based on long non-coding RNA (lncRNA) profiling induced by active AKT, we identify that VAL (Vimentin associated lncRNA, LINC01546), which is directly induced by AKT/STAT3 signaling, functions as a potent pro-metastatic molecule and is essential for active AKT-induced tumor invasion, metastasis and anoikis resistance in lung adenocarcinoma (LAD). Impressively, chemosynthetic siRNAs against VAL shows great therapeutic potential in AKT overactivation-driven metastasis. Interestingly, similar to activated AKT in LAD cells, although unable to induce epithelial-mesenchymal transition (EMT), VAL exerts potent pro-invasive and pro-metastatic effects through directly binding to Vimentin and competitively abrogating Trim16-depedent Vimentin polyubiquitination and degradation. Taken together, our study provides an interesting demonstration of a lncRNA-mediated mechanism for active AKT-driven EMT-independent LAD metastasis and indicates the great potential of targeting VAL or Vimentin stability as a therapeutic approach. The role of long non-coding RNA (lncRNA) in AKT-driven tumor development is unclear. Here, the authors identify VAL (Vimentin associated lncRNA) to be directly induced by AKT/STAT3 signaling and report a lncRNA-mediated mechanism for active AKT-driven EMT-independent lung adenocarcinoma metastasis.
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