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MIEN1 drives breast cancer invasion by regulating cytoskeletal dynamics
Author(s) -
Kpetemey Marilyne,
Vishwanatha Jamboor
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.728.45
Subject(s) - motility , microbiology and biotechnology , filopodia , cytoskeleton , cell migration , biology , actin cytoskeleton , actin , cancer cell , cell , cancer , genetics
Previously known as C35, C17orf37, RDX12 and MGC14832, MIEN1 is a novel gene located in the chromosomal region 17q12‐21. While absent or low in normal tissues, MIEN1 is abundantly expressed in multiple cancers including breast carcinomas. A membrane‐bound signaling adaptor, MIEN1 localizes to the leading edge of migrating cells and promotes migration and invasion by increasing filopodium formation. While MIEN1 is shown to promote motility through filopodia formation, little is known on the mechanisms by which MIEN1 influence the actin cytoskeleton. Exploring underlying mechanisms, we show that MIEN1 associates with the actin cytokeleton during motility and directly influence actin polymerization. Methods We performed immunofluorescence, migration and invasion assays using breast cancer cell lines, MDA‐MB 231 and MCF10CA1a to investigate the mechanisms by which MIEN1 potentiates cell motility. Results Ablation of MIEN1 inhibited cell migration, cell adhesion and altered the phosphorylation status of motility markers. Immunofluorescence staining with FITC‐ conjugated‐phalladoin confirmed that alteration of MIEN1 expression leads to reconfiguration of the actin cytoskeleton in breast cancer cells. Furthermore we found that MIEN1 associates with cytoskeletal proteins involved in motility processes. Conclusion Our results show that MIEN1 is a critical regulator of cell migration and invasion. The importance of MIEN1 in tumor cell dissemination is well established; understanding the molecular mechanisms aiding the processes involved will enable the design of novel and effective treatments for metastatic tumors.