Zhao Huijie, Sun Yuze, Feng Huijing, Cai Jing, Liu Yue, Li Yu, Chen Sijie, Zhou Zhiqing, Du Yuhui, Zeng Xiaofei, Ren Huan, Su Wenmei, Mei Qi, Chen Guoan
Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Department of Human Cell Biology and Genetics, Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.
Int J Biol Sci. 2024 Nov 11;20(15):6056-6072. doi: 10.7150/ijbs.100525. eCollection 2024.
PFKP Phosphofructokinase, Platelet Type isoform), as an essential metabolic enzyme, contributes to the high glycolysis rates seen in cancers while its role in oncogenic pathways, especially from a non-metabolic aspect, is not fully understood. We found that PFKP was highly expressed in NSCLC and was related to poor patient survival. Knockdown of PFKP significantly inhibited cell proliferation, colony formation, invasion, and migration of NSCLC cells. Nanoparticles-mediated PFKP silencing can inhibit tumor growth . Mechanistically, we found that PFKP can bind with AXL and promote its phosphorylation at Y779, thus activating the AXL signaling pathway and promoting MET phosphorylation. In addition, several glycolysis, glutaminolysis, and TCA cycle proteins were downregulated following PFKP silencing. PFKP has an oncogenic role in cancer progression and . Beyond its known role in glycolysis, PFKP also has a non-metabolic function in affecting lung cancer progression by interacting with the AXL-MET axis, thus indicating a potential therapeutic target for lung cancer.
血小板型磷酸果糖激酶（PFKP）作为一种关键的代谢酶，导致癌症中出现高糖酵解率，而其在致癌途径中的作用，尤其是从非代谢方面来看，尚未完全明确。我们发现PFKP在非小细胞肺癌（NSCLC）中高表达，且与患者的不良生存相关。敲低PFKP可显著抑制NSCLC细胞的增殖、集落形成、侵袭和迁移。纳米颗粒介导的PFKP沉默可抑制肿瘤生长。从机制上讲，我们发现PFKP可与AXL结合并促进其在Y779位点的磷酸化，从而激活AXL信号通路并促进MET磷酸化。此外，PFKP沉默后，几种糖酵解、谷氨酰胺分解和三羧酸循环蛋白的表达下调。PFKP在癌症进展中具有致癌作用。除了其在糖酵解中的已知作用外，PFKP还通过与AXL-MET轴相互作用在影响肺癌进展方面具有非代谢功能，因此提示其为肺癌的一个潜在治疗靶点。
