Reprogramming of the tumour microenvironment by stromal PTEN-regulated miR-320 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-02

AUTHORS

A. Bronisz, J. Godlewski, J. A. Wallace, A.S. Merchant, M.O. Nowicki, H. Mathsyaraja, R. Srinivasan, A. J. Trimboli, C. K. Martin, F. Li, L. Yu, S. A. Fernandez, T. Pécot, T. J. Rosol, S. Cory, M. Hallett, M. Park, M. G. Piper, C. B. Marsh, L. D. Yee, R. E. Jimenez, G. Nuovo, S. E. Lawler, E. A. Chiocca, G. Leone, M. C. Ostrowski

ABSTRACT

PTEN (Phosphatase and tensin homolog deleted on chromosome 10) expression in stromal fibroblasts suppresses epithelial mammary tumours, but the underlying molecular mechanisms remain unknown. Using proteomic and expression profiling, we show that Pten loss from mammary stromal fibroblasts activates an oncogenic secretome that orchestrates the transcriptional reprogramming of other cell types in the microenvironment. Downregulation of miR-320 and upregulation of one of its direct targets, ETS2 (v-ets erythroblastosis virus E26 oncogene homolog 2) are critical events in Pten-deleted stromal fibroblasts responsible for inducing this oncogenic secretome, which in turn promotes tumour angiogenesis and tumour-cell invasion. Expression of the Pten-miR-320-Ets2-regulated secretome distinguished human normal breast stroma from tumour stroma and robustly correlated with recurrence in breast cancer patients. This work reveals miR-320 as a critical component of the Pten tumour-suppressor axis that acts in stromal fibroblasts to reprogramme the tumour microenvironment and curtail tumour progression. More... »

PAGES

159-167

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncb2396

    DOI

    http://dx.doi.org/10.1038/ncb2396

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1053604598

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/22179046


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