LINE-1 couples EMT programming with acquisition of oncogenic phenotypes in human bronchial epithelial cells.

ABSTRACT: Although several lines of evidence have established the central role of epithelial-to-mesenchymal-transition (EMT) in malignant progression of non-small cell lung cancers (NSCLCs), the molecular events connecting EMT to malignancy remain poorly understood. This study presents evidence that Long Interspersed Nuclear Element-1 (LINE-1) retrotransposon couples EMT programming with malignancy in human bronchial epithelial cells (BEAS-2B). This conclusion is supported by studies showing that: 1) activation of EMT programming by TGF-?1 increases LINE-1 mRNAs and protein; 2) the lung carcinogen benzo(a)pyrene coregulates TGF-?1 and LINE-1 mRNAs, with LINE-1 positioned downstream of TGF-?1 signaling; and, 3) forced expression of LINE-1 in BEAS-2B cells recapitulates EMT programming and induces malignant phenotypes and tumorigenesis in vivo. These findings identify a TGF?1-LINE-1 axis as a critical effector pathway that can be targeted for the development of precision therapies during malignant progression of intractable NSCLCs.

SUBMITTER: Reyes-Reyes EM 

PROVIDER: S-EPMC5732769 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature