Informace o publikaci
Multiple roles of cytoskeletal proteins transgelins in breast cancer development and metastasis
| Autoři | |
|---|---|
| Rok publikování | 2013 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Transgelin is a cytoplasmic protein, which was inter alia first described in the study looking for new actin associated proteins, whose expression was altered after malignant transformation of cells. In this study, transgelin was shown to gel actin filaments in vitro and to be lost after cell transformation. Transgelin, as well as its sequence homologue transgelin-2 were recently described as deregulated proteins in many types of cancer. Results of our expression studies in breast cancer showed, that transgelin level is decreased, whilst transgelin-2 level is increased in the high grade breast cancer tumors vs. low grade tumors. Moreover, we showed positive correlation between level of both proteins and the presence of lymph node metastasis in breast cancer. Immunohistochemical analysis on tissue microarrays showed cell-type specific expression of transgelin and transgelin-2 in the tumors. Whilst, transgelin-2 was almost strictly expressed in the tumor cells, transgelin was mainly expressed in the cells of the tumor stroma, in which its level increased with the higher grade of the tumor. The mechanism of transgelins function in the cancer is so far poorly understood. We expect and our data from functional studies support this assumption, that transgelins function can be linked to their role in the actin cytoskeleton. The actin cytoskeleton is a dynamic structure, whose deregulation has impact on many cellular processes being important in cancer development and involving proliferation, apoptosis, cell adhesion or migration of cells. Transgelin is associated with F-actin and is important for assembly of actin stress fibers. Using a combination of pull-down purification and SILAC metabolic labeling, we described interaction network of protein transgelin in MCF7 breast cancer cell line. Functional analysis of the proteins from transgelin interacting network using IPA software (Ingenuity systems) confirmed transgelin involvement in the organization actin cytoskeleton. Interestingly, this analysis showed that transgelin interacting partners are involved in RhoA signaling pathway, which is important for stress fiber formation. We studied transgelin role in the migratory behavior of the two breast cancer cell lines BT549 and PMC42. We found that transgelin is able both to promote (in BT549 cells) and to inhibit (in PMC42 cells) cell migration. To further clarify transgelin function in PMC42 and BT549 cells, we studied proteome changes after transgelin silencing in these cells. The lists of proteins with the changed expression after transgelin silencing in each cell line were functionally evaluated using IPA software. The results suggested transgelin role in the cellular assembly and organization, biochemistry of small molecules or apoptosis of the cells. Interestingly, deregulation of the proteins involved in the cell migration was observed just in BT549 not in PMC42 cells, suggesting that determined inhibitory effect of transgelin on migration of the PMC42 cell line was distorted by its effect on other cellular processes. |