Tanaka Yuka, Murata Maho, Oda Yoshinao, Furue Masutaka, Ito Takamichi
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Biomedicines. 2021 Mar 30;9(4):355. doi: 10.3390/biomedicines9040355.
Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, and its incidence is rising because of the aging population. Nectin cell adhesion molecule 4 (NECTIN4) is involved in the progression of tumors and has attracted interest as a potential therapeutic target. However, little is known about the expression and significance of NECTIN4 in cSCC. The aim of this study was to determine the expression and function of NECTIN4 in cSCC. Immunohistological NECTIN4 expression was investigated in tissues from 34 cSCC patients. Using an A431 human SCC cell line, the role of NECTIN4 in the regulation of cell-cell attachment and migration and proliferation was assessed. NECTIN4 was expressed in most cSCC tissues and on the plasma membrane of A431 cells. Silencing of NECTIN4 prevented cell-cell attachment and induced the expression migration-related molecules, leading to an increase in cell migration. Knockdown of NECTIN4 downregulated extracellular signal-regulated kinase signaling, decreased cyclin D1 expression, and inhibited cell proliferation. These results show that NECTIN4 is expressed in cSCC and functions in the regulation of cell-cell interactions, as well as in the migration and proliferation of SCC cells. NECTIN4-targeted therapy may serve as a novel and promising treatment for cSCC.
皮肤鳞状细胞癌（cSCC）是第二常见的皮肤癌，由于人口老龄化，其发病率正在上升。NECTIN细胞粘附分子4（NECTIN4）参与肿瘤进展，并作为潜在治疗靶点引起了关注。然而，关于NECTIN4在cSCC中的表达及意义知之甚少。本研究的目的是确定NECTIN4在cSCC中的表达和功能。对34例cSCC患者的组织进行了免疫组织化学NECTIN4表达研究。使用A431人鳞状细胞癌细胞系，评估NECTIN4在调节细胞间附着、迁移和增殖中的作用。NECTIN4在大多数cSCC组织和A431细胞的质膜上表达。NECTIN4沉默可阻止细胞间附着并诱导迁移相关分子的表达，导致细胞迁移增加。NECTIN4敲低可下调细胞外信号调节激酶信号传导，降低细胞周期蛋白D1表达，并抑制细胞增殖。这些结果表明，NECTIN4在cSCC中表达，并在调节细胞间相互作用以及SCC细胞的迁移和增殖中发挥作用。针对NECTIN4的治疗可能成为cSCC一种新的、有前景的治疗方法。
