Investigating the Mechanism of MenaINV-Driven Metastasis
Technical Report,01 Dec 2012,30 Nov 2015
Massachusetts Institute of Technology Cambridge United States
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Mena, an actin regulatory protein, is upregulated in human breast cancer and is alternatively spliced to produce proteinisoforms with distinct functions during tumor progression. Here, we show that MenaINV promotes synergy between growthfactors and ECM cues, by driving crosstalk downstream of the receptors for these cues, suggesting that Mena supportsmetastasis via chemotaxis and haptotaxis, and that both of these pathways are important for metastatic progression.Furthermore, we show that Mena isoform expression is associated with resistance to Taxol, the front line chemotherapy usedto treat metastatic breast cancer, both in vitro and in vivo. The mechanism driving this resistance is still under investigation.Overall, these data identify new targetable mechanisms by which tumors cells are able to metastasize, and highlight new waysin which resistance to chemotherapy may be predicted and eventually overcome.