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

doi:10.18632/oncotarget.21953

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

Oncotarget. 2017 Oct 23;8(61):103828-103842. doi: 10.18632/oncotarget.21953. eCollection 2017 Nov 28.

Authors

Elsa M Reyes-Reyes¹, Ivan Aispuro¹, Marco A Tavera-Garcia¹, Matthew Field¹, Sara Moore¹, Irma Ramos^{1

2}, Kenneth S Ramos^{1

3

2}

Affiliations

¹ University of Arizona College of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Tucson, AZ, USA.
² Center for Applied Genetics and Genomic Medicine, University of Arizona Health Sciences, Tucson, AZ, USA.
³ University of Arizona Cancer Center, Tucson, AZ, USA.

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-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.

Keywords: EMT programming; LINE-1; oncogenesis.