Liao Dan, Zeng Saitian, Li Cuifen, Yao Yuhong, Guo Min, Cui Yejia, Huang Haohai
Department of Gynaecology, The Affiliated Dongguan Songshan Lake Central Hospital, Guangdong Medical University, Dongguan, Guangdong, China.
Department of Clinical Laboratory, The Affiliated Dongguan Songshan Lake Central Hospital, Guangdong Medical University, Dongguan, Guangdong, China.
Front Cell Dev Biol. 2025 Jun 26;13:1615454. doi: 10.3389/fcell.2025.1615454. eCollection 2025.
Cervical cancer is a prevalent malignancy among women, and its pathogenesis is highly complex. Lipid metabolism plays a crucial role in providing sufficient metabolites and energy for the rapid proliferation and progression of tumors, significantly influencing the advancement of cervical cancer. However, the specific lipid metabolism mechanisms remain to be thoroughly investigated. This study aims to elucidate the lipid metabolism mechanisms by which FOXK2 promotes the progression of cervical cancer.
FOXK2 overexpression and knockdown cell lines were constructed, The cell activity and invasion were evaluated using CCK8, Edu, transwell, and flow cytometry. The oxygen consumption rate (OCR) values were detected by the XFe96 analyzer. The expression of fatty acid oxidation (FAO) related genes was analyzed by WB and qRT-PCR. The binding of FOXK2 to mTOR and mTOR to DRP1 was detected by co-immunoprecipitation (CoIP). Ultimately FOXK2-knockdown cells were applied to construct the Xenograft tumors in nude mice, and the relevant experiments were verified .
experiments, our findings demonstrated that FOXK2 enhances the proliferation and invasive capabilities of cervical cancer cells. FOXK2 expression was found to upregulate the expression of CPT1A, a key enzyme involved in FAO while downregulating the expression of critical lipogenic enzymes ACC1 and FASN. FOXK2 was shown to increase the phosphorylation levels of mTOR and interact with both mTOR and DRP1. Mechanistically, FOXK2 promotes lipid metabolic reprogramming in cervical cancer by interacting with the mTOR/DRP1 signaling axis. Furthermore, the role of FOXK2 in regulating lipid metabolism reprogramming in cervical cancer and its effects on the mTOR/DRP1 axis were validated in xenograft tumor models.
FOXK2 interacts with and phosphorylates mTOR, which facilitates the expression of DRP1 and activates the mTOR/DRP1 signaling axis. This activation regulates lipid metabolic reprogramming and promotes the progression of cervical cancer.
宫颈癌是女性中常见的恶性肿瘤，其发病机制高度复杂。脂质代谢在为肿瘤的快速增殖和进展提供足够的代谢产物和能量方面起着关键作用，对宫颈癌的进展有重大影响。然而，具体的脂质代谢机制仍有待深入研究。本研究旨在阐明FOXK2促进宫颈癌进展的脂质代谢机制。
构建FOXK2过表达和敲低细胞系，使用CCK8、Edu、transwell和流式细胞术评估细胞活性和侵袭能力。用XFe96分析仪检测氧消耗率（OCR）值。通过WB和qRT-PCR分析脂肪酸氧化（FAO）相关基因的表达。通过免疫共沉淀（CoIP）检测FOXK2与mTOR以及mTOR与DRP1的结合。最终将FOXK2敲低细胞应用于裸鼠体内构建异种移植瘤，并对相关实验进行验证。
在实验中，我们的研究结果表明FOXK2增强了宫颈癌细胞的增殖和侵袭能力。发现FOXK2表达上调参与FAO的关键酶CPT1A的表达，同时下调关键的脂肪生成酶ACC1和FASN的表达。FOXK2被证明可增加mTOR的磷酸化水平，并与mTOR和DRP1相互作用。机制上，FOXK2通过与mTOR/DRP1信号轴相互作用促进宫颈癌中的脂质代谢重编程。此外，在异种移植瘤模型中验证了FOXK2在调节宫颈癌脂质代谢重编程中的作用及其对mTOR/DRP1轴的影响。
FOXK2与mTOR相互作用并使其磷酸化，这促进了DRP1的表达并激活了mTOR/DRP1信号轴。这种激活调节脂质代谢重编程并促进宫颈癌的进展。
