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 Ramos

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 - Jan 1 2017

Fingerprint

Non-Small Cell Lung Carcinoma
Epithelial Cells
Phenotype
Retroelements
Messenger RNA
Critical Pathways
Benzo(a)pyrene
Carcinogens
Neoplasms
Carcinogenesis
Lung
Proteins
Therapeutics

Keywords

  • EMT programming
  • LINE-1
  • Oncogenesis

ASJC Scopus subject areas

  • Oncology

Cite this

LINE-1 couples EMT programming with acquisition of oncogenic phenotypes in human bronchial epithelial cells. / Reyes-Reyes, Elsa M.; Aispuro, Ivan; Tavera-Garcia, Marco A.; Field, Matthew; Moore, Sara; Ramos, Irma; Ramos, Kenneth.

In: Oncotarget, Vol. 8, No. 61, 01.01.2017, p. 103828-103842.

Research output: Contribution to journalArticle

Reyes-Reyes, Elsa M. ; Aispuro, Ivan ; Tavera-Garcia, Marco A. ; Field, Matthew ; Moore, Sara ; Ramos, Irma ; Ramos, Kenneth. / LINE-1 couples EMT programming with acquisition of oncogenic phenotypes in human bronchial epithelial cells. In: Oncotarget. 2017 ; Vol. 8, No. 61. pp. 103828-103842.
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