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

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 TGF1-LINE-1 axis as a critical effector pathway that can be targeted for the development of precision therapies during malignant progression of intractable NSCLCs.

published proceedings

  • Oncotarget

author list (cited authors)

  • Reyes-Reyes, E. M., Aispuro, I., Tavera-Garcia, M. A., Field, M., Moore, S., Ramos, I., & Ramos, K. S.

complete list of authors

  • Reyes-Reyes, Elsa M||Aispuro, Ivan||Tavera-Garcia, Marco A||Field, Matthew||Moore, Sara||Ramos, Irma||Ramos, Kenneth S

publication date

  • January 1, 2017 11:11 AM