Department of Internal Medicine 1, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China.
Department of Internal Medicine 4, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China.
Bioengineered. 2022 May;13(5):12532-12547. doi: 10.1080/21655979.2022.2076497.
Recent studies have shown that the expression of integrin-linked kinase (ILK) was related to the occurrence, development, and malignant progression of esophageal squamous cell carcinoma (ESCC). However, research on the relationship between ILK and the chemosensitivity of ESCC has to date not been reported. The present study found that ILK was highly expressed in ESCC cell lines, and the overexpression of ILK in ESCC cells reduced the incidence of cell apoptosis and alleviated the cytotoxicity on cells induced by cisplatin (CDDP). Inversely, ILK knockdown increased CDDP-induced apoptosis and had an inhibitive effect on the malignant phenotype of ESCC, including cell proliferation, invasion, and migration. In addition, ILK knockdown in ESCC cells inhibited the expression of beta (β)-catenin and activated the wingless/integrated (Wnt) signaling pathway. Furthermore, cellular MYC (c-MYC) and Cylin D1 were the target genes of the Wnt signaling pathway. Rescue experiments showed that the overexpression of β-catenin reversed a tumor's inhibition and apoptosis abilities induced by ILK knockdown. In conclusion, ILK potentially reduced the CDDP sensitivity of ESCC cells by influencing the activity of the Wnt/β-catenin signaling pathway.
最近的研究表明整合素连接激酶（ILK）的表达与食管鳞状细胞癌（ESCC）的发生、发展和恶性进展有关。然而，目前为止，有关 ILK 与 ESCC 化疗敏感性之间关系的研究尚未报道。本研究发现 ILK 在 ESCC 细胞系中高表达，ILK 在 ESCC 细胞中的过表达降低了细胞凋亡的发生率，并减轻了顺铂（CDDP）对细胞的细胞毒性。相反，ILK 敲低增加了 CDDP 诱导的细胞凋亡，并对 ESCC 的恶性表型具有抑制作用，包括细胞增殖、侵袭和迁移。此外，ESCC 细胞中 ILK 的敲低抑制了β-连环蛋白（β-catenin）的表达并激活了无翅型整合素（Wnt）信号通路。此外，细胞 MYC（c-MYC）和 Cylin D1 是 Wnt 信号通路的靶基因。挽救实验表明，β-catenin 的过表达逆转了由 ILK 敲低引起的肿瘤抑制和细胞凋亡能力。综上所述，ILK 通过影响 Wnt/β-catenin 信号通路的活性降低了 ESCC 细胞对 CDDP 的敏感性。
