ArticleCell death & disease2022
Zeb1-induced metabolic reprogramming of glycolysis is essential for macrophage polarization in breast cancer.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 2 of them syntheses that pooled it.
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Who cites it
134 citing papers in PubMed, 2 syntheses or guidelines pooled it, 152 citations in OpenAlex.
- Aberrant Energy Metabolism in Tumors and Potential Therapeutic Targets.Genes, chromosomes & cancer · 2024Pooled it
- Research progresses and hotspots on glucose metabolic reprogramming in breast cancer: a bibliometric analysis over the past two decades.Frontiers in oncology · 2024Pooled it
- Targeting the SELP/PSGL1 axis reprograms M2 macrophages and enhances anti-PD-1 efficacy in gastric cancer.Oncogene · 2026Article
- Next-generation macrophage engineering in cancer therapy: From TAM reprogramming to CAR-macrophages.Molecular therapy. Nucleic acids · 2026Review
- The Brucella effector protein BtpB facilitates STAT3 activation to regulate polarization in macrophages during infection.Veterinary research · 2026Article
- GPI: A pan-cancer biomarker integrating genetic alterations, immune infiltration, and therapeutic response prediction.Global medical genetics · 2026Article
- Role of ZEB1 in angiogenesis and therapeutic potential (Review).International journal of molecular medicine · 2026Review
- PI3K/AKT signaling pathway: molecular crossroads in tumorigenesis and therapeutic innovation.Signal transduction and targeted therapy · 2026Review
- TRIM26 triggers ferroptosis via ZEB1 degradation to suppress nasopharyngeal carcinoma progression.Journal of molecular histology · 2026Article
- Integrating whole-genome resequencing data reveals adaptive selection signatures under extreme environments of goat populations in China.BMC genomics · 2026Article
- The glycolysis-H4K12la-PKM2 positive feedback loop drives M2 polarization of macrophages in colorectal cancer.Clinical epigenetics · 2026Article
- Integrin-mediated mechanotransduction in the tumor microenvironment: macrophage-centered signaling mechanisms and immune remodeling.Journal of translational medicine · 2026Review
- Flavonoid compounds from Shenrong Guben Huanshao Pill alleviates senescence-associated mitochondrial dysfunction through NDUFV2 and LDHB mediated metabolic reprogramming.Journal of pharmaceutical analysis · 2026Article
- Single-cell transcriptomics reveals glycolytic heterogeneity and identifies STC2 as a key regulator of metabolic reprogramming in osteosarcoma.Molecular and cellular biochemistry · 2026Article
- SASH1 Inhibits Gastric Cancer Progression by Regulating YAP1-Mediated Metabolic Reprogramming.Applied biochemistry and biotechnology · 2026Article
- P2RY6Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Tumor microenvironment-responsive ARRDC4: unveiling the tumor-suppressive pathway in colorectal cancer progression.Cancer cell international · 2026Article
- Identification of key genes related to macrophages and metabolic reprogramming in myocardial infarct based on single-cell and bulk transcriptomics data and experimental validation.BMC cardiovascular disorders · 2026Article
- Breast Cancer Milieu Maneuvers Cancer-Associated Macrophages to Synergize Neoplastic Repertoires.Cancers · 2026Review
- PRSS23 functions downstream of ZEB1 to promote esophageal squamous cell carcinoma progression by driving M2 polarization of tumor associated macrophages.Molecular and cellular biochemistry · 2026Article
74 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aerobic glycolysis (the Warburg effect) has been demonstrated to facilitate tumor progression by producing lactate, which has important roles as a proinflammatory and immunosuppressive mediator. However, how aerobic glycolysis is directly regulated is largely unknown. Here, we show that ectopic Zeb1 directly increases the transcriptional expression of HK2, PFKP, and PKM2, which are glycolytic rate-determining enzymes, thus promoting the Warburg effect and breast cancer proliferation, migration, and chemoresistance in vitro and in vivo. In addition, Zeb1 exerts its biological effects to induce glycolytic activity in response to hypoxia via the PI3K/Akt/HIF-1α signaling axis, which contributes to fostering an immunosuppressive tumor microenvironment (TME). Mechanistically, breast cancer cells with ectopic Zeb1 expression produce lactate in the acidic tumor milieu to induce the alternatively activated (M2) macrophage phenotype through stimulation of the PKA/CREB signaling pathway. Clinically, the expression of Zeb1 is positively correlated with dysregulation of aerobic glycolysis, accumulation of M2-like tumor-associated macrophages (TAMs) and a poor prognosis in breast cancer patients. In conclusion, these findings identify a Zeb1-dependent mechanism as a driver of breast cancer progression that acts by stimulating tumor-macrophage interplay, which could be a viable therapeutic target for the treatment of advanced human cancers.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.