Targeting the crosstalks of Wnt pathway with Hedgehog and Notch for cancer therapy. (April 2019)

• Record Type: Journal Article
• Authors: Chatterjee, Sharmistha; Sil, Parames C.
• Is Part Of: Pharmacological research. Volume 142(2019)
• Page Start: 251
• Page End: 261
• Publication Date: 2019-04
• Subjects: α-SMA alpha smooth muscle actin -- ADAM a disintegrin and metalloproteinase -- AML acute myeloid leukemia -- APC adenomatous polyposis coli -- β-TrCP beta-transducin repeats-containing proteins -- BCC basal cell carcinoma -- BCL9 B-cell CLL/Lymphoma 9 -- BMP bone morphogenetic protein -- CBF core binding factor -- CK1 α casein kinase 1 alpha -- CRD-BP coding region determinant binding protein -- CSCs cancer stem cells -- CSL, CBF-1 suppressor of hairless Lag-2 -- CML chronic myeloid leukemia -- Ci cubitus interruptus -- CTNNB1 catenin beta-1 (also known as β-catenin) -- DKK3 Dickkopf-related protein 3 -- DHH desert Hedgehog -- DLL homeotic protein distal-less -- Dsh dishevelled -- EMT epithelial to mesenchymal transition -- EZH2 enhancer of zeste homolog 2 -- FDA food and drug administration -- FGF fibroblast growth factor -- Fz frizzled -- GLI glioma-associated oncogene -- GSK3 glycogen synthase kinase 3 -- HH Hedgehog -- HIF-1α hypoxia-inducible factor 1-alpha -- HOXC6 homeobox C6 -- IGF insulin-like growth factor 1 -- IHH Indian Hedgehog -- JNK c-Jun N-terminal kinase -- KRAS v-Ki-as2 Kirsten Rat sarcoma viral oncogene -- LATS2 large tumor suppressor kinase 2 -- LEF lymphoid enhancer-binding factor 1 -- LRP low density lipoprotein receptor-related protein 1 -- MAML mastermind-like protein -- MYF5 myogenic Factor 5 -- NECD notch extra-cellular domain -- NF-κB nuclear factor kappa B -- NICD notch intra-cellular domain -- NTC notch transcriptional complex -- PAF platelet-activating factor -- PP2A protein phosphatase 2 A -- PTCH patched -- PTEN phosphatase and tensin homolog -- RAC1 Ras-related C3 botulinum toxin substrate 1 -- RBP retinol-binding protein -- RNF43 ring-finger protein 43 -- ROCK Rho-associated protein kinase -- ROS reactive oxygen species -- S6K1 Ribosomal protein S6 kinase beta-1 -- sFRP1 secreted frizzled-related protein 1 -- SMARCB1 SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 -- SMO smoothened -- SOXG Sry-related HMG box SRP1 stress-related protein 1 -- SWI/SNF switch/sucrose non-fermentable tace tumor necrosis factor alpha-convertase TCF T-cell factor -- TERT telomerase reverse transcriptase -- TGF-β transforming growth factor beta -- TNBC triple negative breast cancer -- TNF-α tumor necrosis factor alpha -- YAP/TAZ yes-associated protein/tafazzin -- ZNRF3 zinc and ring finger 3; Wnt -- Hedgehog -- Notch -- Crosstalk -- Cancer stem cells -- Combination therapy in cancer; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2019.02.027
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Wnt, Hedgehog and Notch pathways affecting various phases of cancer. Abstract: Wnt pathway is an evolutionarily conserved signaling pathway determining patterning of animal embryos, cell fate, cell polarity, and a substantial role in the origin and maintenance of stem cells. It has been found to crosstalk with two other major developmental pathways, Hedgehog and Notch, in many embryological development cascades and in maintaining stemness of stem cells Research has shown that all the three pathways are potent in inducing tumorigenesis, driving tumor progression and aiding epithelial to mesenchymal transition in malignant cells, apart from maintaining cancer stem cells population inside the tumor tissue. Cancer stem cells are thought to aid in the process of tumor relapse, as they survive therapy by displaying drug resistance and then repopulating tumor tissues. Hence the role of these crosstalks in cancer is under intensive research. Inhibition of all the three pathways individually have resulted in tumor regression, but not optimally, as treatment failure and cancer relapse have been found to occur. Hence, instead of targeting a single pathway, targeting the crosstalk network could be a better alternative to conventional cancer treatment. Also, elimination of both tumor cells as well as cancer stem cells implies a reduced chance of relapse. Drugs developed to target these crosstalking networks, when used in combinatorial therapy, can potentially increase the efficacy of the therapy to a very large extent.