IGFBP2 Promotes Proliferation and Glycolysis of Endometrial Cancer by Regulating PKM2/HIF-1α Axis

Overview

Journal Cancer Sci

Specialty Oncology

Date 2025 Jan 6

PMID 39761954

Authors

Yuxi Jin

Meng Qi

Lulu Si

Xiaojing Shi

Mingbo Cai

Hanlin Fu

Yana Liu

Ruixia Guo

Affiliations

Soon will be listed here.

Abstract

Endometrial cancer (EC) is a worldwide gynecologic malignancies, with a remarking increase of incidence and mortality rates in recent years. Growing evidence indicates that glucose metabolism reprogramming is the most representative metabolic signature of tumor cells and exploring its modulatory function in EC development will promote identifying potential EC therapeutic targets. IGFBP2 is an insulin-like growth factor binding protein which is closely associated with a variety of metabolic diseases. However, its biological role in EC and its effects on glucose metabolism remain unclear. In this study, we demonstrated that IGFBP2 was highly expressed in EC tissues and correlated with poor prognosis. Overexpression of IGFBP2 promoted proliferation and glycolysis in EC cells, whereas IGFBP2 knockdown had the opposite effect. Mechanistically, IGFBP2 directly interacted with PKM2, inducing weakened PKM2 protein degradation, and knockdown IGFBP2 expression prevented the translocation of PKM2 to the nucleus. Additionally, IGFBP2 expression was upregulated under the condition of hypoxia which directly regulated by transcriptional activation of HIF-1α. Finally, the role of the IGFBP2/PKM2/HIF-1α axis in EC tumor growth was confirmed in vivo using mouse xenograft models. Taken together, the current study identifies IGFBP2 as an upstream activator of PKM2-driven proliferation and glycolysis in EC cells, providing a promising therapeutic target for EC.

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