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PCK2 Promotes Ribosome Biogenesis in Cervical Cancer Cells via Interaction with hnRNPK
Fang Yang1, Mengjuan Zhu2, Jiaqi Qiu2
1The First Affiliated Hospital of Soochow University, Soochow University, #899 Pinghai Road, Gusu District, Suzhou, China.
Abstract:
Mitochondrial phosphoenolpyruvate carboxykinase (PCK2) is a key rate-limiting enzyme in gluconeogenesis. In cancers originating from non-gluconeogenic organs, PCK2 often exhibits a pro-tumorigenic effect, primarily through metabolic reprogramming. Through cancer database analyses and validation using tissue samples from patients with cervical cancer, we found that PCK2 exhibits oncogenic activity in cervical cancer and is localized in ribosomes within cervical cancer cells. A combination of in vitro cellular experiments, in vivo xenograft models, molecular biology techniques, transcriptomic and proteomic sequencing revealed a novel mechanism by which PCK2 drives cervical cancer progression: PCK2 enhances translational efficiency by directly interacting with the ribosome-associated protein hnRNPK. This newly identified oncogenic role of PCK2 expands our understanding of its function and provides a mechanistic foundation for its contribution to tumorigenesis in cancers arising from non-gluconeogenic tissues.
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