| First Author | Ghose S | Year | 2015 |
| Journal | PLoS One | Volume | 10 |
| Issue | 1 | Pages | e0116338 |
| PubMed ID | 25635825 | Mgi Jnum | J:225654 |
| Mgi Id | MGI:5693992 | Doi | 10.1371/journal.pone.0116338 |
| Citation | Ghose S, et al. (2015) delta-Catenin activates Rho GTPase, promotes lymphangiogenesis and growth of tumor metastases. PLoS One 10(1):e0116338 |
| abstractText | delta-Catenin, an adherens junctions protein, is not only involved in early development, cell-cell adhesion and cell motility in neuronal cells, but it also plays an important role in vascular endothelial cell motility and pathological angiogenesis. In this study, we report a new function of delta-catenin in lymphangiogenesis. Consistent with expression of delta-catenin in vascular endothelial cells, we detected expression of the gene in lymphatic endothelial cells (LECs). Ectopic expression of delta-catenin in LECs increased cell motility and lymphatic vascular network formation in vitro and lymphangiogenesis in vivo in a Matrigel plug assay. Conversely, knockdown of delta-catenin in LECs impaired lymphangiogenesis in vitro and in vivo. Biochemical analysis shows that delta-catenin regulates activation of Rho family small GTPases, key mediators in cell motility. delta-catenin activates Rac1 and Cdc42 but inhibits RhoA in LECs. Notably, blocking of Rac1 activation impaired delta-catenin mediated lymphangiogenesis in a Matrigel assay. Consistently, loss of delta-catenin in mice inhibited the growth of tumor metastases. Taken together, these findings identify a new function of delta-catenin in lymphangiogenesis and tumor growth/metastasis, likely through modulation of small Rho GTPase activation. Targeting delta-catenin may offer a new way to control tumor metastasis. |
