α5-nAChR/ADAM10 信号通过 STAT3 激活介导尼古丁相关的皮肤黑色素瘤进展。
α5-nAChR/ADAM10 signaling mediates nicotine-related cutaneous melanoma progression via STAT3 activation.
发表日期:2024 May 25
作者:
Xiangying Li, Xianguang Meng, Huiping Fan, Yan Wang, Yanfei Jia, Jing Jiao, Xiaoli Ma
来源:
PHARMACOLOGY & THERAPEUTICS
摘要:
皮肤黑色素瘤(SKCM)是死亡率最高的皮肤恶性肿瘤,其发病率在全球范围内呈上升趋势。吸烟是黑色素瘤预后不良的独立标志。 α5-烟碱乙酰胆碱受体(α5-nAChR)是尼古丁受体之一,参与SKCM细胞的增殖、迁移和侵袭。据报道,尼古丁可促进解整合素和金属蛋白酶 10 (ADAM10) 的表达,这是参与黑色素瘤进展的关键基因。在这里,我们探讨了尼古丁相关皮肤黑色素瘤中 α5-nAChR 和 ADAM10 之间的联系。 α5-nAChR 表达与 ADAM10 表达和 SKCM 中较低的生存率相关。 α5-nAChR 通过 STAT3 介导尼古丁诱导的 ADAM10 表达。 α5-nAChR/ADAM10信号轴参与SKCM细胞的干性和迁移。此外,在尼古丁相关小鼠同种移植组织中,α5-nAChR 表达与 ADAM10 表达、EMT 标记表达和干性标记表达相关。这些结果表明 α5-nAChR/ADAM10 信号通路在尼古丁诱导的黑色素瘤进展中的作用。© 2024。作者获得 Springer-Verlag GmbH 德国(Springer Nature 旗下公司)的独家许可。
Skin cutaneous melanoma (SKCM) is the skin malignancy with the highest mortality rate, and its morbidity rate is on the rise worldwide. Smoking is an independent marker of poor prognosis in melanoma. The α5-nicotinic acetylcholine receptor (α5-nAChR), one of the receptors for nicotine, is involved in the proliferation, migration and invasion of SKCM cells. Nicotine has been reported to promote the expression of a disintegrin and metalloproteinase 10 (ADAM10), which is the key gene involved in melanoma progression. Here, we explored the link between α5-nAChR and ADAM10 in nicotine-associated cutaneous melanoma. α5-nAChR expression was correlated with ADAM10 expression and lower survival in SKCM. α5-nAChR mediated nicotine-induced ADAM10 expression via STAT3. The α5-nAChR/ADAM10 signaling axis was involved in the stemness and migration of SKCM cells. Furthermore, α5-nAChR expression was associated with ADAM10 expression, EMT marker expression and stemness marker expression in nicotine-related mice homograft tissues. These results suggest the role of the α5-nAChR/ADAM10 signaling pathway in nicotine-induced melanoma progression.© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.