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-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.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/627063 |
| Date | 23 October 2017 |
| Creators | Reyes-Reyes, Elsa M., Aispuro, Ivan, Tavera-Garcia, Marco A., Field, Matthew, Moore, Sara, Ramos, Irma, Ramos, Kenneth S. |
| Contributors | Univ Arizona, Coll Med, Div Pulm Allergy Crit Care & Sleep Med, Univ Arizona, Canc Ctr, Univ Arizona Hlth Sci, Ctr Appl Genet & Genom Med |
| Publisher | IMPACT JOURNALS LLC |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | Article |
| 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). |
| Relation | http://www.oncotarget.com/fulltext/21953 |
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