Inhibition of endothelial Cdk5 reduces tumor growth by promoting non-productive angiogenesis

摘要: Therapeutic success of VEGF-based anti-angiogenic tumor therapy is limited due to resistance. Thus, new strategies for cancer based on novel targets are urgently required. Our previous in vitro work suggested that small molecule Cdk5 inhibitors affect angiogenic processes such as endothelial migration and proliferation. Moreover, we recently uncovered a substantial role the development lymphatic vessels. Here pin down vivo impact inhibition angiogenesis elucidate underlying mechanism order judge potential anti-cancer target. By use endothelial-specific knockout mouse models various cell assays including human xenograft models, show knockdown results excessive but non-productive during also tumors, which subsequently leads growth. As disrupted Notch function by reducing generation active intracellular domain (NICD) modulates Notch-dependent proliferation sprouting, propose Dll4/Notch driven signaling hub an important promising mechanistic target Cdk5. In fact, can sensitize tumors conventional treatment shown models. summary our data set stage drugable inhibit Notch-driven condensing view therapy.