Figure 1.

Notch signaling in cancer cells. (A) When binding to a Notch ligand (ex. Dll4), gamma-secretase cleaves Notch receptor to release NICD from plasma membrane. Once the NICD is translocated to nucleus, transcription of downstream genes (ex. HES1, HEY1) is activated. Activation of Notch signaling in cancer cells promotes cell proliferation; (B) Notch signaling is usually not activated without binding to the Notch ligand; however, (C) gain-of-function mutation of Notch was reported in some cancer cells, and Notch signaling is constitutively activated to promote proliferation and survival of these cells; (D) Blockade of Dll4/Notch signaling in tumor cells using Dll4 antagonist (yellow triangle) increases the density of poorly functioned blood vessels (red line with black dot), resulting in reduction of blood flow in the tumor to suppress cancer cell growth.