The ras homolog gene family, member A (RhoA) pathway mediates MMP-2 and MMP-9-independent invasive behavior in a triple-negative breast cancer cell line.

TitleThe ras homolog gene family, member A (RhoA) pathway mediates MMP-2 and MMP-9-independent invasive behavior in a triple-negative breast cancer cell line.
Publication TypeJournal Article
Year of Publication2013
AuthorsFagan-Solis KD, Schneider SS, Pentecost BT, Bentley BA, Otis CN, Gierthy JF, Arcaro KF
JournalJ Cell Biochem
Date Published2013 Jun
ISSN1097-4644
Abstract

Breast cancer is a heterogeneous disease that varies in its biology and response to therapy. A foremost threat to patients is tumor invasion and metastasis, with the greatest risk among patients diagnosed with triple-negative and/or basal-like breast cancers. A greater understanding of the molecular mechanisms underlying cancer cell spreading is needed as 90% of cancer-associated deaths result from metastasis. We previously demonstrated that the tamoxifen-selected, MCF-7 derivative, TMX2-28, lacks expression of estrogen receptor α (ERα) and is highly invasive, yet maintains an epithelial morphology. The present study was designed to further characterize TMX2-28 cells and elucidate their invasion mechanism. We found that TMX2-28 cells do not express human epidermal growth factor receptor 2 (HER2) and progesterone receptor (PR), in addition to lacking ERα, making the cells triple-negative. We then determined that TMX2-28 cells lack expression of active matrix metalloproteinases (MMPs) -1, MMP-2, MMP-9, and other genes involved in epithelial-mesenchymal transition (EMT) suggesting that TMX2-28 may not utilize mesenchymal invasion. In contrast, TMX2-28 cells have high expression of RhoA, a protein known to play a critical role in amoeboid invasion. Blocking RhoA activity with the RhoA pathway specific inhibitor H-1152, or a RhoA specific siRNA, resulted in inhibition of invasive behavior. Collectively, these results suggest that TMX2-28 breast cancer cells exploit a RhoA-dependent, proteolytic-independent invasion mechanism. Targeting the RhoA pathway in triple-negative, basal-like breast cancers that have a proteolytic-independent invasion mechanism may provide therapeutic strategies for the treatment of patients with increased risk of metastasis. J. Cell. Biochem. © 2012 Wiley Periodicals, Inc.

DOI10.1002/jcb.24480
Alternate JournalJ. Cell. Biochem.
PubMed ID23255405