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Metastasis tumor-associated protein 2 enhances metastatic behavior and is associated with poor outcomes in estrogen receptor-negative breast cancer.

TitleMetastasis tumor-associated protein 2 enhances metastatic behavior and is associated with poor outcomes in estrogen receptor-negative breast cancer.
Publication TypeJournal Article
Year of Publication2013
AuthorsCovington, Kyle R., Brusco Lauren, Barone Ines, Tsimelzon Anna, Selever Jennifer, Corona-Rodriguez Arnoldo, Brown Powel, Kumar Rakesh, Hilsenbeck Susan G., and Fuqua Suzanne A. W.
JournalBreast cancer research and treatment
Date Published2013 Sep 28
ISSN1573-7217
AbstractMetastasis remains a major clinical problem in breast cancer. One family of genes previously linked with metastasis is the metastasis tumor-associated (MTA) family, with members MTA1 enhancing and MTA3 inhibiting cancer metastasis. We have previously found that MTA2 enhances anchorage-independent growth in estrogen receptor α (ERα) breast cancers, and, in combination with other genes, performed as a predictive biomarker in ERα-positive breast cancer. We therefore hypothesized that MTA2 enhances breast cancer progression. To test this, cell growth, soft-agar colony formation, migration, and in vivo metastasis were examined in MTA2-overexpressing and Vector control transfected ERα-negative breast cancer cells. Pathways regulating cell-cell interaction, adhesion, and signaling through the Rho pathway were also investigated. Effects of the inhibition of the Rho pathway using a Rho Kinase inhibitor were assessed in soft-agar colony formation and motility assays in MTA2-overexpressing cells. MTA2 expression was associated with poor prognostic markers, and levels of MTA2 were associated with increased risk of early recurrence in retrospective analyses. MTA2 overexpression was associated with enhanced metastasis, and pathways regulating cell-cell interactions in vitro and in vivo. Most critically, MTA2-enhanced motility could be blocked by inhibiting Rho pathway signaling. We present the novel finding that MTA2 defined a subset of ERα-negative patients with a particularly poor outcome.
DOI10.1007/s10549-013-2709-5
Alternate JournalBreast Cancer Res. Treat.


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