Publication:
miR-17-92/p38α dysregulation enhances Wnt signal and selects Lgr6+ cancer stem cell like cells during human lung adenocarcinoma progression

Date
04/05/16
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American Association for Cancer Research
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Research Project
RG51968/RG57589
Research Project
RG52191
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Defining the molecular and cellular roots of lung cancer relapse after initial treatment remains an imperative to improve survival. Here we report that the lung stem cell marker Lgr6 becomes enriched in non-small cell lung cancer (NSCLC) cells during malignant progression. Lgr6+ NSCLC cells displayed self-renewal and differentiation properties along with a higher tumorigenic potential. Mechanistic investigations suggested that a defective repression of the miR-17-92 gene cluster was responsible for evolution of a selection for outgrowth of Lgr6+ NSCLC cells. High levels of expression of miR-19 family members were found to target and downregulate levels of p38α kinase, providing a specific survival signal for Lgr6+ cells as mediated by increased Wnt/ß-catenin activity. Our results identify a specific stem-like cell population in NSCLC with increased malignant potential, the elucidation of which may enable earlier prognosis and possibly the development of more effective targeted treatments.
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