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

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

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Although several lines of evidence have established the central role of epithelialto- 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-β1 increases LINE-1 mRNAs and protein; 2) the lung carcinogen benzo(a)pyrene coregulates TGF-β1 and LINE- 1 mRNAs, with LINE-1 positioned downstream of TGF-β1 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 TGFβ1- LINE-1 axis as a critical effector pathway that can be targeted for the development of precision therapies during malignant progression of intractable NSCLCs.

Original languageEnglish (US)
Pages (from-to)103828-103842
Number of pages15
JournalOncotarget
Volume8
Issue number61
DOIs
StatePublished - 2017

Keywords

  • EMT programming
  • LINE-1
  • Oncogenesis

ASJC Scopus subject areas

  • Oncology

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