The regulation of actin cytoskeleton by c-Myb: potential implications for site-specific metastases of breast cancer
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| Year of publication | 2014 |
| Type | Conference abstract |
| MU Faculty or unit | |
| Citation | |
| Description | During metastasis, tumor cells adapt their motility, pericellular proteolysis, cell-cell and cell-matrix adhesion to suit their changeable environment. Metastatic cells thus undergo dramatic molecular changes by remodeling their actin cytoskeleton. The actin cytoskeleton serves as a scaffold for signaling and a connection with the extracellular environment and its regulation is critical for tumor cells to colonize distant organs. The actin-binding ERM (ezrin, radixin, moesin) proteins are key regulators of the interactions between the cell membrane and cortical cytoskeleton. The ERM proteins participate in diverse processes including endocytosis/exocytosis, adhesion and migration, and contribute to disease progression in clinical cancers. We demonstrated previously that transcription factor c-Myb reduced the growth of the transplanted mammary tumors and their spontaneous pulmonary metastases. As moesin has been previously identified as a potential target of c-Myb transactivation, we investigated the expression of ERM proteins in the Myb-overexpressing breast cancer cells. We observed that the ectopic c-Myb expression decreased the level of moesin and radixin in 4T1 cells. However, no differences in moesin and radixin subcellular distribution were noticed between Myb-overexpressing and control cells. Finally, we analyzed MYB, MSN and RDX expression in human breast carcinomas with organ-specific metastases using publically available microarray data. While MYB expression is significantly lower in tumors metastasizing to lungs, MSN and RDX mRNA levels are significantly higher in tumors with metastases in lungs compared to tumors with extra-lung metastases. We hypothesize that suppressed expression of ERM proteins by c-Myb might (by means of differential regulation of cortical actin and/or membrane domains organization and/or signaling) contribute to reduced growth and site-selective metastases of the MYB-overexpressing breast tumors. |
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