Wnt/Notch/Hedgehog

Notch signalling is a primordial, evolutionarily conserved cell-fate-determination pathway that has great relevance to multiple aspects of cancer biology, from CSCs to angiogenesis to tumour immunity.The Notch signalling pathway is complex and multifaceted, reflecting its roles in diverse functional activities. The pathway comprises five canonical Notch ligands (Delta-like ligand 1 [DLL1], DLL3 and DLL4, and Jagged1 and Jagged2) and four Notch receptor paralogues (Notch1–4).
HH signalling pathway is implicated in tissue-patterning during embryonic development and the repair of normal tissues, and epithelial-to-mesenchymal transition.Binding of HH ligands—Sonic hedgehog (SHH), Indian hedgehog (IHH), or Desert hedgehog (DHH)—relieves the inhibitory effect of their Patched (PTCH) transmembrane receptors on Smoothened (SMO), which is also located in the cell membrane.
Wnt-signalling cascade comprises three major pathways: the canonical Wnt pathway, which involves activation of β-catenin-T-cell-specific transcription factor (TCF)–lymphoid enhancer-binding factor (LEF) transactivation complex and is implicated in tumorigenesis; the noncanonical planar-cell polarity pathway, which regulates the cytoskeleton; and the noncanonical Wnt–calcium pathway, which regulates intracellular calcium levels.Of these pathways, canonical Wnt signalling is the best understood and its inhibition has been the focus of intensive research in cancer and other diseases. Indeed, along with the Notch and HH pathways, suppression of Wnt signalling has led to the development of agents that hold promise to interfere with carcinogenesis, tumour invasiveness and metastasis.