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PMID:22984505
| Citation |
Iida, J, Dorchak, J, Lehman, JR, Clancy, R, Luo, C, Chen, Y, Somiari, S, Ellsworth, RE, Hu, H, Mural, RJ and Shriver, CD (2012) FH535 Inhibited Migration and Growth of Breast Cancer Cells. PLoS ONE 7:e44418 |
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| Abstract |
There is substantial evidence indicating that the WNT signaling pathway is activated in various cancer cell types including breast cancer. Previous studies reported that FH535, a small molecule inhibitor of the WNT signaling pathway, decreased growth of cancer cells but not normal fibroblasts, suggesting this pathway plays a role in tumor progression and metastasis. In this study, we tested FH535 as a potential inhibitor for malignant phenotypes of breast cancer cells including migration, invasion, and growth. FH535 significantly inhibited growth, migration, and invasion of triple negative (TN) breast cancer cell lines (MDA-MB231 and HCC38) in vitro. We demonstrate that FH535 was a potent growth inhibitor for TN breast cancer cell lines (HCC38 and MDA-MB-231) but not for other, non-TN breast cancer cell lines (MCF-7, T47D or SK-Br3) when cultured in three dimensional (3D) type I collagen gels. Western blotting analyses suggest that treatment of MDA-MB-231 cells with FH535 markedly inhibited the expression of NEDD9 but not activations of FAK, Src, or downstream targets such as p38 and Erk1/2. We demonstrated that NEDD9 was specifically associated with CSPG4 but not with β1 integrin or CD44 in MDA-MB-231 cells. Analyses of gene expression profiles in breast cancer tissues suggest that CSPG4 expression is higher in Basal-type breast cancers, many of which are TN, than any other subtypes. These results suggest not only a mechanism for migration and invasion involving the canonical WNT-signaling pathways but also novel strategies for treating patients who develop TN breast cancer. |
| Links |
PubMed Online version:10.1371/journal.pone.0044418 |
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Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
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| GO:2000446: regulation of macrophage migration inhibitory factor signaling pathway |
ECO:0000316: |
UniProtKB:Q6UVK1
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P |
Figure 6. The results of the paper suggest that NEDD9 promotes tumor cell migration and invasion. These results suggest that NEDD9 plays a key role in facilitating MDA-MB-231 cell migration, invasion, and growth. |
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