The Impact of Notch Signaling for Carcinogenesis and Progression of Nonmelanoma Skin Cancer: Lessons Learned from Cancer
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, respectiv
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The Impact of Notch Signaling for Carcinogenesis and Progression of Nonmelanoma Skin Cancer: Lessons Learned from Cancer Stem Cells, Tumor Angiogenesis, and Beyond Jörg Reichrath and Sandra Reichrath
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
J. Reichrath (*) Department of Dermatology, Saarland University Medical Center, Homburg, Germany e-mail: [email protected] S. Reichrath Department of Dermatology, Saarland University Medical Center, Homburg, Germany School of Health Professions, Saarland University Medical Center, Homburg, Germany
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. Keywords
Angiogenesis · Cancer · Cancer stem cells · Cancer treatment · Notch · Nonmelanoma skin cancer · Notch signaling · Notch pathway · Skin cancer · Tumor angiogenesis
Abbreviations AE AK Ang
Adverse event Actinic keratosis Angiopoietin
© Springer Nature Switzerland AG 2021 J. Reichrath, S. Reichrath (eds.), Notch Signaling in Embryology and Cancer, Advances in Experimental Medicine and Biology 1287, https://doi.org/10.1007/978-3-030-55031-8_9
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BCC Basal cell carcinoma Ancient Friends, Revisited: A Short BMP Bone morphogenic protein Introduction to the Relevance cKO Conditional knockout of Notch Signaling for Skin CSC Cancer stem cell and Cancer CSL CBF-1, Su (H), Lag-1-type transcription factor (also termed RBP-J) Although most types of nonmelanoma skin canDBD DNA-binding domain cers (NMSCs) are not documented in the cancer Dll Delta-like registries of most countries, there is no doubt that E Embryonic day they are since many decades the most common FGF Fibroblast growth factor malignancies worldwide (Reichrath and GLI1 Glioma-associated oncogene homolog 1 Reichrath 2012a; Reichrath and Rass 2014). Hes Hairy and enhancer of
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