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The review summarizes how keratinocyte contributions shape basal cell carcinoma, cutaneous squamous cell carcinoma, and melanoma, highlighting emerging findings, potential biomarkers, and therapeutic targets.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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Dainese-Marque, Virginie Garcia, Nathalie Andrieu-Abadie * and Joëlle Riond *  \nCitation: Dainese-Marque, O.; Garcia, V.; Andrieu-Abadie, N.; Riond, J. Contribution of Keratinocytes in Skin Cancer Initiation and Progression. Int.  \nJ. Mol. Sci. 2024, 25, 8813. [https://](https://)[ ](https://)[doi.org/10.3390/ijms25168813](doi.org/10.3390/ijms25168813)  \nAcademic Editor: Cosimo Di Raimondo  \nReceived: 19 July 2024  \nRevised: 10 August 2024  \nAccepted: 11 August 2024  \nPublished: 13 August 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \nUniversité de Toulouse, Inserm, CNRS, Université Toulouse III-Paul Sabatier, Centre de Recherches en Cancérologie de Toulouse, 31037 Toulouse, France  \n* [Correspondence: nathalie.andrieu@inserm.fr](Correspondence: nathalie.andrieu@inserm.fr) (N.A.-A.); [joelle.riond@inserm.fr](joelle.riond@inserm.fr) (J.R.)  \nAbstract: Keratinocytes are major cellular components of the skin and are strongly involved in its homeostasis. Oncogenic events, starting mainly from excessive sun exposure, lead to the dysregulation of their proliferation and differentiation programs and promote the initiation and progression of non-melanoma skin cancers (NMSCs) . Primary melanomas, which originate from melanocytes, initiate and develop in close interaction with keratinocytes, whose role in melanoma initiation, progression, and immune escape is currently being explored. Recent studies highlighted, in particular, unexpected modes of communication between melanocytic cells and keratinocytes, which may be of interest as sources of new biomarkers in melanomagenesis or potential therapeutic targets. This review aims at reporting the various contributions of keratinocytes in skin basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and melanoma, with a greater focus on the latter in order to highlight some recent breakthrough findings. The readers are referred to recent reviews when contextual information is needed.  \nKeywords: keratinocyte; melanoma; microenvironment; skin carcinoma; tumor invasion  \n1. Introduction  \nKeratinocytes are the major cellular components of the epidermis, the outer layer of the skin. As the main interface with the external environment, the skin acts as a physical barrier to protect our body from external aggressions, including pathogens, physical agents, chemicals, and ultraviolet (UV) radiation, and prevents dehydration of the underlying tissues. These functions are ensured by a highly organized architecture in which epidermal keratinocytes play a pivotal role. Keratinocytes maintain epidermal homeostasis through reciprocal interactions with neighboring keratinocytes to form an organized and cohesive epidermal structure, with melanocytes to maintain the UV-protective function of the “epidermal unit”, and with immune cells to detect and eradicate pathogen threats. These interactions are finely regulated by cell–cell adhesion, cell-matrix adhesion, and paracrine signaling. Here, we summarize how keratinocytes self-interact and interact with melanocytes within the epidermal microenvironment, and how dysregulations of their cellular functions and interactions contribute to skin carcinomas and melanoma.  \n2. Skin Architecture  \nThe skin is organized into three layers: the epidermis and the dermis separated by a semi-permeable basal lamina, and the hypodermis (Figure 1A) . The epidermis is a stratified epithelium with adnexal structures (hair follicles, sweat glands, and sebaceous glands) extending to the dermis. Epidermal stem cells continuously self-renew and result in dividing kerat","cbCaiptOOLwienPg","https://ap.wps.com/l/cbCaiptOOLwienPg","pdf",2239903,27,"English","# 1. Introduction\n# 2. Skin Architecture","[{\"question\":\"What is the main role of keratinocytes in the skin according to the article?\",\"answer\":\"Keratinocytes are major components of the epidermis and are strongly involved in maintaining skin homeostasis through organized architecture and regulated cellular interactions.\"},{\"question\":\"How does sun exposure contribute to skin cancer via keratinocytes?\",\"answer\":\"Excessive sun exposure initiates oncogenic events that dysregulate keratinocyte proliferation and differentiation, promoting initiation and progression of non-melanoma skin cancers.\"},{\"question\":\"Why are keratinocytes important in melanoma development and immune escape?\",\"answer\":\"Primary melanomas develop through close interaction between melanocytes and keratinocytes, and keratinocytes are involved in melanoma initiation, progression, and immune escape.\"}]","Contribution of Keratinocytes in Skin Cancer Initiation and Progression - Review | PDF",1790003633,68]