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

Gaigai Shen,

Shiya Liu,

Yuanting Cao

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Фев. 10, 2025

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

Язык: Английский

Metabolic reprogramming and therapeutic resistance in primary and metastatic breast cancer DOI Creative Commons
Shan Liu,

Xingda Zhang,

Wenzheng Wang

и другие.

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Ноя. 21, 2024

Metabolic alterations, a hallmark of cancer, enable tumor cells to adapt their environment by modulating glucose, lipid, and amino acid metabolism, which fuels rapid growth contributes treatment resistance. In primary breast metabolic shifts such as the Warburg effect enhanced lipid synthesis are closely linked chemotherapy failure. Similarly, metastatic lesions often display distinct profiles that not only sustain but also confer resistance targeted therapies immunotherapies. The review emphasizes two major aspects: mechanisms driving in both how unique environments sites further complicate treatment. By targeting vulnerabilities at stages, new strategies could improve efficacy existing provide better outcomes for cancer patients.

Язык: Английский

Процитировано

18

Hsp90 Promotes Gastric Cancer Cell Metastasis and Stemness by Regulating the Regional Distribution of Glycolysis‐Related Metabolic Enzymes in the Cytoplasm DOI Creative Commons
Shiya Liu,

Gaigai Shen,

Xuanyu Zhou

и другие.

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Июнь 14, 2024

Heat-shock protein 90 (Hsp90) plays a crucial role in tumorigenesis and tumor progression; however, its mechanism of action gastric cancer (GC) remains unclear. Here, the Hsp90 GC metabolism is focus this research. High expression tissues can interact with glycolysis, collectively affecting prognosis clinical samples. Both vitro vivo experiments demonstrate that able to regulate migration stemness properties cells. Metabolic phenotype analyses indicate influences glycolytic metabolism. Mechanistically, interacts glycolysis-related enzymes, forming multienzyme complexes enhance glycolysis efficiency yield. Additionally, binds cytoskeleton-related proteins, regulating regional distribution enzymes at cell margin lamellar pseudopods. This effect could lead local increase efficient energy supply from further promoting epithelial-mesenchymal transition (EMT) metastasis. In summary, Hsp90, through interaction metabolic related forms multi-enzyme regulates by dynamic cytoskeletal adjustments, thereby These conclusions also support potential for combined targeted approach involving cytoskeleton therapy.

Язык: Английский

Процитировано

4

More than Just Protein Folding: The Epichaperome, Mastermind of the Cancer Cell DOI Creative Commons
Haneef Ahmed Amissah, Maxwell Hubert Antwi,

Tawfeek Ahmed Amissah

и другие.

Cells, Год журнала: 2025, Номер 14(3), С. 204 - 204

Опубликована: Янв. 30, 2025

The epichaperome, a dynamic and integrated network of chaperone proteins, extends its roles beyond basic protein folding to stabilization intracellular signal transduction orchestrating multitude cellular processes critical for tumor survival. In this review, we explore the multifaceted delving into diverse locations, factors that modulate formation function, liquid–liquid phase separation, key signaling crosstalk pathways it regulates, including metabolism transduction. We further highlight techniques isolating identifying epichaperome networks, pitfalls, opportunities. Further, review profound implications cancer treatment therapy design, underscoring need strategic engineering hinges on comprehensive insight structure workings across heterogeneous cell subpopulations in milieu. By presenting holistic view epichaperome’s functions mechanisms, aim underscore potential as target novel anti-cancer strategies, revealing is not merely piece machinery but mastermind facilitates malignant phenotype.

Язык: Английский

Процитировано

0

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

Gaigai Shen,

Shiya Liu,

Yuanting Cao

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Фев. 10, 2025

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

Язык: Английский

Процитировано

0