Figure 1.

Schematic for NOTCH signaling in cancer cells. Upon the binding of NOTCH ligands (JAG1, JAG2, DLL1, DLL3, and DLL4) on adjacent cells, such as stromal cells or other cancer cells, NOTCH (NOTCH1–NOTCH4) on cancer cells can be activated through proteolytic cleavage (by ADAM proteinase and γ-secretase) to release its intracellular domain (NICD), which in turn translocates to the nucleus, where it forms transcription complexes with transcription cofactors (the blue shapes) to regulate cell-context-dependent transcription.