Guo Luopei, Li Chunbo, Guo Jingjing, Qiu Junjun, Hua Keqin
Obstetrics and Gynecology Hospital of Fudan University Shanghai, China.
Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai, China.
Am J Cancer Res. 2023 Jun 15;13(6):2376-2391. eCollection 2023.
This study aimed to investigate whether CKAP2 could promote cervical cancer (CC) progression by modulating the tumor microenvironment (TME) via NF-κB signaling. The communication between cervical cancer cells and the TME, including THP-1 and HUVECs, was tested. Gain- and loss-of-function assays were performed to elucidate the role of CKAP2 in cervical cancer progression. Western blot analysis was exploited to investigate the potential involved mechanism involved. Here, we reported that cervical cancer tissues were enriched with macrophages and microvessels. CKAP2 increased the tumor-promoting macrophage population. The overexpression of CKAP2 not only promoted endothelial cell viability and tube formation but also increased vascular permeability, and vice versa. Moreover, CKAP2 promoted cervical cancer progression via NF-κB signaling. This effect could be blocked by the NF-κB signaling inhibitor JSH-23. Our findings indicated that CKAP2 could promote cervical cancer progression by modulating the TME via NF-κB signaling.
本研究旨在探究细胞角蛋白关联蛋白2（CKAP2）是否可通过核因子κB（NF-κB）信号通路调节肿瘤微环境（TME）来促进宫颈癌（CC）进展。检测了宫颈癌细胞与TME（包括THP-1细胞和人脐静脉内皮细胞（HUVECs））之间的相互作用。进行了功能获得和功能缺失实验以阐明CKAP2在宫颈癌进展中的作用。利用蛋白质免疫印迹分析来研究潜在的相关机制。在此，我们报告宫颈癌组织富含巨噬细胞和微血管。CKAP2增加了具有促肿瘤作用的巨噬细胞数量。CKAP2的过表达不仅促进内皮细胞活力和管腔形成，还增加血管通透性，反之亦然。此外，CKAP2通过NF-κB信号通路促进宫颈癌进展。这种作用可被NF-κB信号通路抑制剂JSH-23阻断。我们的研究结果表明，CKAP2可通过NF-κB信号通路调节TME来促进宫颈癌进展。
