Wu Man, Zhang Yingying, Wang Xuanhui, Zhou Yijia
Key Laboratory for Reproductive Medicine of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
J Cell Mol Med. 2025 Mar;29(6):e70522. doi: 10.1111/jcmm.70522.
Cervical cancer (CC) remains a major health challenge with high mortality rates due to chemoresistance and immune escape. However, the underlying mechanisms remain unclear. We investigated the role of TAB2 in CC using cisplatin-resistant and parental cell lines. Cell proliferation, migration, sphere formation and T cell-mediated killing assays were performed. Western blot and qRT-PCR analysed protein and mRNA expression. NF-κB pathway involvement was examined using the BAY 11-7082 inhibitor. TAB2 expression was significantly elevated in cisplatin-resistant CC cells. TAB2 overexpression promoted chemoresistance and immune escape through NF-κB pathway activation. Conversely, TAB2 knockdown or NF-κB inhibition sensitised resistant cells to cisplatin and enhanced T cell-mediated killing. The resistant phenotype could be rescued by restoring PD-L1 expression. Our findings reveal TAB2 as a critical regulator of both chemoresistance and immune escape in CC through NF-κB pathway activation. This suggests TAB2 as a potential therapeutic target for overcoming treatment resistance in CC.
宫颈癌（CC）由于化疗耐药和免疫逃逸导致死亡率居高不下，仍然是一项重大的健康挑战。然而，其潜在机制尚不清楚。我们使用顺铂耐药细胞系和亲本细胞系研究了TAB2在宫颈癌中的作用。进行了细胞增殖、迁移、成球和T细胞介导的杀伤试验。通过蛋白质印迹法和qRT-PCR分析蛋白质和mRNA表达。使用BAY 11-7082抑制剂检测NF-κB通路的参与情况。TAB2在顺铂耐药的宫颈癌细胞中表达显著升高。TAB2过表达通过激活NF-κB通路促进化疗耐药和免疫逃逸。相反，敲低TAB2或抑制NF-κB可使耐药细胞对顺铂敏感，并增强T细胞介导的杀伤作用。恢复PD-L1表达可挽救耐药表型。我们的研究结果表明，TAB2通过激活NF-κB通路，是宫颈癌化疗耐药和免疫逃逸的关键调节因子。这表明TAB2是克服宫颈癌治疗耐药性的潜在治疗靶点。
