title: δ-Catenin activates Rho GTPase, promotes lymphangiogenesis and growth of tumor metastases.
abstract: δ-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 δ-catenin in lymphangiogenesis. Consistent with expression of δ-catenin in vascular endothelial cells, we detected expression of the gene in lymphatic endothelial cells (LECs). Ectopic expression of δ-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 δ-catenin in LECs impaired lymphangiogenesis in vitro and in vivo. Biochemical analysis shows that δ-catenin regulates activation of Rho family small GTPases, key mediators in cell motility. δ-catenin activates Rac1 and Cdc42 but inhibits RhoA in LECs. Notably, blocking of Rac1 activation impaired δ-catenin mediated lymphangiogenesis in a Matrigel assay. Consistently, loss of δ-catenin in mice inhibited the growth of tumor metastases. Taken together, these findings identify a new function of δ-catenin in lymphangiogenesis and tumor growth/metastasis, likely through modulation of small Rho GTPase activation. Targeting δ-catenin may offer a new way to control tumor metastasis.
authors: Center for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India.
authors: Sampa
authors: S
authors: Ghose
authors: Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, 21702, United States of America.
authors: Yongfen
authors: Y
authors: Min
authors: Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, 21702, United States of America.
authors: P Charles
authors: PC
authors: Lin
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000473:pathology*; D051177:Catenins / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology; D004789:Enzyme Activation; D008175:Lung Neoplasms / Q000556:secondary*; D042583:Lymphangiogenesis; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D047368:Tumor Burden; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D000095002:Delta Catenin
chemical_list: D051177:Catenins; D020741:rho GTP-Binding Proteins; D000095002:Delta Catenin
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