CPNE1 mediates glycolysis and metastasis of breast cancer through activation of PI3K/AKT/HIF-1α signaling

• Published in: Pathology, research and practice Vol. 248; p. 154634
• Main Authors: Cao, Jingying, Cao, Renxian, Liu, Yiqi, Dai, Tao
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.08.2023
• Subjects: AKT; CPNE1; Glycolysis; PI3K; Triple-negative breast cancer; CPNE1; Glycolysis; AKT; PI3K; Triple-negative breast cancer
• ISSN: 0344-0338; 1618-0631
• DOI: 10.1016/j.prp.2023.154634

CPNE1 regulates multiple signaling pathways and can stimulate cell proliferation and differentiation by activating the AKT-mTOR signaling pathway. In addition, CPNE1 is associated with various cancers; however, its role in breast cancer, particularly in TNBC, has not been fully elucidated. Our study aimed to reveal the impact of the CPNE1/PI3K/AKT/HIF-1α axis on TNBC. We first measured the expression of CPNE1 in the tumor tissues of TNBC patients and examined its prognostic value. Subsequently, we used sh-CPNE1 and overexpression vectors to transfect TNBC cell lines and analyzed cell viability, migration, and invasive abilities using colony formation and CCK-8 assays. Metabolites were analyzed through metabolomics. We found that higher expression of CPNE1 predicted poor prognosis in TNBC patients. Knockdown of CPNE1 reduced the viability, migration, invasion, and proliferation capabilities of TNBC cells. Furthermore, metabolomics analysis showed that glucose metabolism was the most dominant pathway, and knockdown of CPNE1 significantly limited the glycolytic activity of TNBC cells. We verified these conclusions in mouse models. Additionally, we overexpressed CPNE1 and treated TNBC cell lines with a PI3K inhibitor (LY294002). The results indicated that CPNE1 promoted aerobic glycolysis in TNBC cells through the PI3K/AKT/HIF-1α signaling pathway. This suggests that CPNE1 regulates cell glycolysis and participates in the development of TNBC. Our study may provide a new therapeutic target for TNBC treatment.