HSP90 co-regulates the formation and nuclear distribution of the glycolytic output complex to promote resistance and poor prognosis in gastric cancer patients

• DOI: 10.1186/s12967-025-06196-w
• Publication Date: 2025-02-10T13:43:13Z
• Authors: Gaigai Shen; Shiya Liu; Yuanting Cao; Zihao Chen; Guanghui Wang; Long Yu; Lixin Sun; Yuliang Ran
• Keywords: Immunoprecipitation

Resistance to treatment is a critical factor contributing poor prognosis in gastric cancer patients. HSP90 has emerged as promising therapeutic target; however, its role regulating tumor metabolic pathways, particularly glycolysis, remains poorly understood, which limits clinical application. We identified proteins that directly interact with using immunoprecipitation (IP) followed by mass spectrometry. The relationship between and glycolysis was further investigated through transcriptomic analyses vitro experiments. Mechanistic insights were obtained spectrometry, co-immunoprecipitation (Co-IP) assays, drug sensitivity tests, bioinformatics analyses. Additionally, we developed scoring system based on data evaluate prognostic significance association resistance Our multi-omics studies revealed regulates influences the stemness properties of cells. Mechanistically, facilitates assembly glycolytic multi-enzyme complex, termed HGEO enhances metabolism. formation multienzyme complex comprising key enzymes including PGK1, PKM2, ENO1, LDHA, thereby facilitating production final products. refer this "HSP90-Glycolytic Output Complex" (HGEO Complex). quantified phenomenon (HGScore), finding patients high HGScore exhibited more malignant signatures, increased treatment, poorer prognoses. Furthermore, demonstrated localized nucleus, regulated nuclear lamina protein LMNA, contributes adverse outcomes. In experiments indicated inhibiting sensitizes cells chemotherapy. findings suggest LMNA mediated localization enhancing traits mechanisms cancer. Targeting pathway may offer novel strategy improve