Thyroid transcription factor 1 enhances cellular statin sensitivity via perturbing cholesterol metabolism View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-06

AUTHORS

Shao-Chiang Lai, Cody A. Phelps, Aleena M. Short, Sucharita M. Dutta, David Mu

ABSTRACT

We have discovered an unexpected connection between a critical lung development and cancer gene termed thyroid transcription factor 1 (TTF-1 also known as NKX2-1) and cholesterol metabolism. Our published work implicates that TTF-1 positively regulates miR-33a which is known to repress ATP-binding cassette transporter 1 (ABCA1) and thus its cholesterol efflux activity. We set out to demonstrate that a higher TTF-1 expression would presumably inhibit cholesterol efflux and consequently raise intracellular cholesterol level. Surprisingly, raising TTF-1 expression actually lowers intracellular cholesterol level, which, we believe, is attributed to a direct transactivation of ABCA1 by TTF-1. Subsequently, we show that lung cancer cells primed with a TTF-1-driven decrease of cholesterol were more vulnerable to simvastatin, a frequently prescribed cholesterol biosynthesis inhibitor. In view of the fact that pathologists routinely interrogate human lung cancers for TTF-1 immunopositivity to guide diagnosis and the prevalent use of statins, TTF-1 should be further investigated as a putative biomarker of lung cancer vulnerability to statins. More... »

PAGES

3290-3300

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41388-018-0174-7

DOI

http://dx.doi.org/10.1038/s41388-018-0174-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1101558229

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29551766


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