Abstract
Since many decades, nonmelanoma skin cancer (NMSCs) is the most common malignancy worldwide. Basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) are the major types of NMSCs, representing approximately 70% and 25% of these neoplasias, respectively. Because of their continuously rising incidence rates, NMSCs represent a constantly increasing global challenge for healthcare, although they are in most cases nonlethal and curable (e.g., by surgery). While at present, carcinogenesis of NMSC is still not fully understood, the relevance of genetic and molecular alterations in several pathways, including evolutionary highly conserved Notch signaling, has now been shown convincingly. The Notch pathway, which was first developed during evolution in metazoans and that was first discovered in fruit flies (Drosophila melanogaster), governs cell fate decisions and many other fundamental processes that are of high relevance not only for embryonic development, but also for initiation, promotion, and progression of cancer. Choosing NMSC as a model, we give in this review a brief overview on the interaction of Notch signaling with important oncogenic and tumor suppressor pathways and on its role for several hallmarks of carcinogenesis and cancer progression, including the regulation of cancer stem cells, tumor angiogenesis, and senescence.
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Abbreviations
- AE:
-
Adverse event
- AK:
-
Actinic keratosis
- Ang:
-
Angiopoietin
- BCC:
-
Basal cell carcinoma
- BMP:
-
Bone morphogenic protein
- cKO:
-
Conditional knockout
- CSC:
-
Cancer stem cell
- CSL:
-
CBF-1, Su (H), Lag-1-type transcription factor (also termed RBP-J)
- DBD:
-
DNA-binding domain
- Dll:
-
Delta-like
- E:
-
Embryonic day
- FGF:
-
Fibroblast growth factor
- GLI1:
-
Glioma-associated oncogene homolog 1
- Hes:
-
Hairy and enhancer of split
- Hf:
-
Hair follicle
- HPV:
-
Human papilloma virus
- Hrt:
-
Hes-related transcription factor
- IP:
-
Intermediate progenitor
- IPC:
-
Intermediate progenitor cell
- JAG:
-
Jagged
- KO:
-
Knockout
- MAML:
-
Mastermind-like
- MET:
-
Mesenchymal-to-epithelial transition
- MMP:
-
Matrix metalloproteinase
- MR:
-
Mortality rate
- NID:
-
Notch intracellular domain
- NMSC:
-
Nonmelanoma skin cancer
- NO:
-
Nitric oxide
- OD:
-
Oligomerization domain
- PDGF:
-
Platelet-derived growth factor
- PDT:
-
Photodynamic therapy
- PTCH:
-
Patched
- RBP-J:
-
Recombinant recognition sequence-binding protein at the Jκ site (also termed CSL)
- SCC:
-
Squamous cell carcinoma
- Sema:
-
Semaporin
- Shh:
-
Sonic hedgehog
- SMC:
-
Smooth muscle cell
- TA:
-
Transactivation domain
- TLR:
-
Toll-like-receptor
- UVR:
-
Ultraviolet radiation
- VEGF:
-
Vascular endothelial growth factor
- Wnt:
-
Wingless-related integration site
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Reichrath, J., Reichrath, S. (2021). The Impact of Notch Signaling for Carcinogenesis and Progression of Nonmelanoma Skin Cancer: Lessons Learned from Cancer Stem Cells, Tumor Angiogenesis, and Beyond. In: Reichrath, J., Reichrath, S. (eds) Notch Signaling in Embryology and Cancer. Advances in Experimental Medicine and Biology, vol 1287. Springer, Cham. https://doi.org/10.1007/978-3-030-55031-8_9
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