LINE-1 couples EMT programming with acquisition of oncogenic phenotypes in human bronchial epithelial cells
AuthorReyes-Reyes, Elsa M.
Tavera-Garcia, Marco A.
Ramos, Kenneth S.
AffiliationUniv Arizona, Coll Med, Div Pulm Allergy Crit Care & Sleep Med
Univ Arizona, Canc Ctr
Univ Arizona Hlth Sci, Ctr Appl Genet & Genom Med
MetadataShow full item record
PublisherIMPACT JOURNALS LLC
CitationLINE-1 couples EMT programming with acquisition of oncogenic phenotypes in human bronchial epithelial cells 2017, 8 (61) Oncotarget
Rights© Reyes-Reyes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0).
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AbstractAlthough 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-beta 1 increases LINE-1 mRNAs and protein; 2) the lung carcinogen benzo(a)pyrene coregulates TGF-beta 1 and LINE-1 mRNAs, with LINE-1 positioned downstream of TGF-beta 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 beta 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.
VersionFinal published version
SponsorsUniversity of Arizona Health Sciences; University of Arizona Diversity and Inclusion Award; Career Development Award
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