Molecular signaling cascades involved in nonmelanoma skin carcinogenesis.
Molecular signaling cascades involved in nonmelanoma skin carcinogenesis.
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DOI：
10.1042/bcj20160471
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发表时间：
2016-10-01
期刊：
影响因子：
--
通讯作者：
Shantz LM
中科院分区：
文献类型：
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作者：
Feehan RP;Shantz LM
非黑色素瘤皮肤癌(NMSC)是世界范围内最常见的癌症，其发病率持续上升，部分原因是器官移植受者和服用光敏药物的高危群体人数增加。NMSC最重要的危险因素是来自阳光的紫外线辐射(UVR)，特别是UVB，它是导致DNA损伤、光老化和皮肤恶性转化的主要原因。紫外线照射后细胞凋亡的激活可以消除可能存在致癌突变的不可逆转的受损细胞。然而，UVR也激活了信号级联，促进了这些潜在癌细胞的生存，导致了肿瘤的发生。因此，UVR在皮肤中诱导的应激反应是多方面的，需要协调激活许多控制DNA损伤修复、炎症和导致细胞存活或死亡的激酶介导的信号转导的通路。这篇综述主要集中在对UVR和随后的细胞变化做出反应的中央信号机制。考虑到NMSC的流行和由此带来的医疗负担，这些途径中的许多都为继续研究化学预防和化疗提供了有希望的靶点。
Non-melanoma skin cancer (NMSC) is the most common cancer world-wide and the incidence continues to rise, in part due to increasing numbers in high-risk groups such as organ transplant recipients and those taking photosensitizing medications. The most significant risk factor for NMSC is ultraviolet radiation (UVR) from sunlight, specifically UVB, which is the leading cause of DNA damage, photoaging, and malignant transformation in the skin. Activation of apoptosis following UVR exposure allows the elimination of irreversibly damaged cells that may harbor oncogenic mutations. However, UVR also activates signaling cascades that promote the survival of these potentially cancerous cells, resulting in tumor initiation. Thus, the UVR-induced stress response in the skin is multi-faceted and requires coordinated activation of numerous pathways controlling DNA damage repair, inflammation, and kinase-mediated signal transduction that lead to either cell survival or cell death. This review focuses on the central signaling mechanisms that respond to UVR and the subsequent cellular changes. Given the prevalence of NMSC and the resulting health care burden, many of these pathways provide promising targets for continued study aimed at both chemoprevention and chemotherapy.