Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, 325027, Wenzhou, Zhejiang, China.
Department of Obstetrics and Gynecology, Taizhou Women and Children's Hospital of Wenzhou Medical University, 317599, Taizhou, Zhejiang, China.
BMC Cancer. 2024 Mar 4;24(1):296. doi: 10.1186/s12885-024-12030-1.
The effect of DOCK1 gene on the biological behavior of endometrial carcinoma cells and its related pathway has not been reported.
The immunohistochemical method and western blot were utilized to analyze DOCK1 protein expression in endometrial tissues and cells, respectively. CCK-8, BrdU, transwell and flow cytometry were performed to analyze the effect of DOCK1 expression changes on the viability, proliferation, invasion, migration and apoptosis of endometrial cancer cells, respectively. The effects of DOCK1 gene on Bcl-2, MMP9, Ezrin, E-cadherin and c-RAF/ERK1/2 signaling pathway were evaluated by western blot. The xenograft models were constructed to analyze the effect of DOCK1 in vivo.
DOCK1 expression was increased in endometrial cancer tissues and cells compared with those in normal adjacent tissues and cells. DOCK1 knockout could inhibit the malignant biological behavior of endometrial cancer cells, while DOCK1 overexpression played the opposite effect. The expression of E-cadherin was upregulated and those of MMP9, Ezrin, Bcl-2, p-c-RAF (S338) and p-ERK1/2 (T202/Y204) were downregulated after DOCK1 knockout, while DOCK1 overexpression played the opposite effect. Additionally, Raf inhibitor LY3009120 reversed the function of DOCK1 on malignant biological behavior. In vivo experiment results showed that the growth and weight of transplanted tumors in nude mice were inhibited after DOCK1 knockout. The changes of E-cadherin, MMP9, Ezrin and Bcl-2 expressions in the transplanted tumors were consistent with those in vitro.
DOCK1 could enhance the malignant biological behavior of endometrial cancer cells, which might be through c-RAF/ERK1/2 signaling pathways in vitro and in vivo.
DOCK1 基因对子宫内膜癌细胞生物学行为的影响及其相关通路尚未报道。
采用免疫组化法和 Western blot 法分别检测子宫内膜组织和细胞中 DOCK1 蛋白的表达。CCK-8、BrdU、Transwell 和流式细胞术分别分析 DOCK1 表达变化对子宫内膜癌细胞活力、增殖、侵袭、迁移和凋亡的影响。Western blot 法评价 DOCK1 基因对 Bcl-2、MMP9、Ezrin、E-cadherin 和 c-RAF/ERK1/2 信号通路的影响。构建荷瘤模型分析 DOCK1 体内作用。
DOCK1 在子宫内膜癌组织和细胞中的表达高于正常相邻组织和细胞。DOCK1 敲除可抑制子宫内膜癌细胞的恶性生物学行为，而 DOCK1 过表达则发挥相反作用。E-cadherin 表达上调，MMP9、Ezrin、Bcl-2、p-c-RAF（S338）和 p-ERK1/2（T202/Y204）表达下调，DOCK1 过表达则发挥相反作用。此外，Raf 抑制剂 LY3009120 逆转了 DOCK1 对恶性生物学行为的作用。体内实验结果表明，DOCK1 敲除后裸鼠移植瘤的生长和重量受到抑制。移植瘤中 E-cadherin、MMP9、Ezrin 和 Bcl-2 表达的变化与体外一致。
DOCK1 可增强子宫内膜癌细胞的恶性生物学行为，可能通过体外和体内 c-RAF/ERK1/2 信号通路。
