Abstract
Transforming growth factor beta (TGF-β) induces epithelial–mesenchymal transition (EMT) accompanied by cellular differentiation and migration. Despite extensive transcriptomic profiling, identification of TGF-β-inducible, EMT-specific genes during metastatic progression of lung cancer remains elusive. Here, we functionally validate a previously described post-transcriptional pathway by which TGF-β modulates expression of interleukin-like EMT inducer (ILEI), and EMT itself. We show that poly r(C)-binding protein 1 (PCBP1) binds ILEI transcript and repress its translation. TGF-β activation leads to phosphorylation at serine-43 of PCBP1 by protein kinase Bβ/Akt2, inducing its release from the ILEI transcript and translational activation. Modulation of hnRNP E1 expression modification altered TGF-β-mediated reversal of translational silencing of ILEI transcripts and EMT. Furthermore, ILEI could induce, as well as maintain, CD24lowCD44high subpopulation in A549 cells treated with TGF-β, which might explain its capability to induce metastatic progression. These results thus validate the existence of an evolutionary conserved TGF-β-inducible post-transcriptional regulon that controls EMT and subsequent metastatic progression of lung cancer.
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Qi Song and Wei Sheng are co-first authors.
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Song, Q., Sheng, W., Zhang, X. et al. ILEI drives epithelial to mesenchymal transition and metastatic progression in the lung cancer cell line A549. Tumor Biol. 35, 1377–1382 (2014). https://doi.org/10.1007/s13277-013-1188-y
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DOI: https://doi.org/10.1007/s13277-013-1188-y