Lumican effectively regulates the estrogen receptors-associated functional properties of breast cancer cells, expression of matrix effectors and epithelial-to-mesenchymal transition.

Date publication

mars 2017

Journal

Scientific reports

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BREZILLON Stéphane

Tous les auteurs :
Karamanou K, Franchi M, Piperigkou Z, Perreau C, Maquart FX, Vynios DH, Brézillon S

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/28332606

Résumé

Lumican is a small leucine-rich proteoglycan that has been shown to contribute in several physiological processes, but also to exert anticancer activity. On the other hand, it has been recently shown that knockdown of the estrogen receptor α (ERα) in low invasive MCF-7 (ERα+) breast cancer cells and the suppression of ERβ in highly aggressive MDA-MB-231 (ERβ+) cells significantly alter the functional properties of breast cancer cells and the gene expression profile of matrix macromolecules related to cancer progression and cell morphology. In this report, we evaluated the effects of lumican in respect to the ERs-associated breast cancer cell behaviour, before and after suppression of ERs, using scanning electron and confocal microscopies, qPCR and functional assays. Our data pinpointed that lumican significantly attenuated cell functional properties, including proliferation, migration and invasion. Furthermore, it modified cell morphology, inducing cell-cell junctions, evoked EMT/MET reprogramming and suppressed the expression of major matrix effectors (matrix metalloproteinases and EGFR) implicated in breast cancer progression. The effects of lumican were found to be related to the type of breast cancer cells and the ERα/β type. These data support the anticancer activity of lumican and open a new area for the pharmacological targeting of the invasive breast cancer.

Mots clés

Breast Neoplasms, genetics, Cell Line, Tumor, Cellular Reprogramming, genetics, Epithelial-Mesenchymal Transition, drug effects, Extracellular Matrix, metabolism, Female, Gene Expression Profiling, Gene Knockout Techniques, Humans, Lumican, pharmacology, MCF-7 Cells, Proto-Oncogene Proteins c-met, genetics, RNA, Small Interfering, genetics, Receptors, Estrogen, metabolism

Référence

Sci Rep. 2017 Mar;7:45138