ArticleAmerican journal of translational research2019
The TGFβ1-FOXM1-HMGA1-TGFβ1 positive feedback loop increases the cisplatin resistance of non-small cell lung cancer by inducing G6PD expression.
Article in American journal of translational research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 30 citations in OpenAlex.
- Does Glucose-6-Phosphate Dehydrogenase Deficiency Correlate with Increased Sensitivity to Cisplatin? A Case Report and a Narrative Literature Review.International journal of molecular sciences · 2026Review
- FOXM1 induces therapy resistance and inhibits apoptosis in a variety of human cancers.Cell death & disease · 2026Review
- Protein Acetylation in Age-Related Macular Degeneration: Mechanisms, Roles, and Therapeutic Perspectives.Investigative ophthalmology & visual science · 2025Review
- Therapeutic Chemoresistance in Ovarian Cancer: Emerging Hallmarks, Signaling Mechanisms and Alternative Pathways.Current medicinal chemistry · 2025Review
- Blockade of glucose-6-phosphate dehydrogenase induces immunogenic cell death and accelerates immunotherapy.Journal for immunotherapy of cancer · 2024Article
- HMGA1 promotes the progression of esophageal squamous cell carcinoma by elevating TKT-mediated upregulation of pentose phosphate pathway.Cell death & disease · 2024Article
- Single-cell decoding of drug induced transcriptomic reprogramming in triple negative breast cancers.Genome biology · 2024Article
- Novel FOXM1 inhibitor STL001 sensitizes human cancers to a broad-spectrum of cancer therapies.Cell death discovery · 2024Article
- Article
- The Emerging Roles of the Metabolic Regulator G6PD in Human Cancers.International journal of molecular sciences · 2023Review
- Musashi-2 (MSI2) promotes neuroblastoma tumorigenesis through targeting MYC-mediated glucose-6-phosphate dehydrogenase (G6PD) transcriptional activation.Medical oncology (Northwood, London, England) · 2023Article
- HMGA1 and FOXM1 Cooperate to Promote G2/M Cell Cycle Progression in Cancer Cells.Life (Basel, Switzerland) · 2023Article
- HMGA1 gene expression level in cancer tissue and blood samples of non-small cell lung cancer (NSCLC) patients: preliminary report.Molecular genetics and genomics : MGG · 2022Article
- FOXM1 Inhibition Enhances the Therapeutic Outcome of Lung Cancer Immunotherapy by Modulating PD-L1 Expression and Cell Proliferation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Review
- TGF-β signaling in the tumor metabolic microenvironment and targeted therapies.Journal of hematology & oncology · 2022Review
- Prognostic Significance ofInternational journal of molecular sciences · 2022Article
- Molecular mechanisms associated with chemoresistance in esophageal cancer.Cellular and molecular life sciences : CMLS · 2022Review
- High Mobility Group A1 (HMGA1): Structure, Biological Function, and Therapeutic Potential.International journal of biological sciences · 2022Review
- Recent findings in the regulation of G6PD and its role in diseases.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Platinum-based chemotherapy is still widely applied for the treatment of advanced non-small cell lung cancer (NSCLC). However, acquired chemoresistance compromises the curative effect of this drug. In this study, we found that glucose-6-phosphate dehydrogenase (G6PD), a critical enzyme of the pentose phosphate pathway, contributed to cisplatin resistance in NSCLC. The experimental results showed that transforming growth factor beta 1 (TGFβ1) increased the expression of G6PD by activating the forkhead box protein M1-high mobility group AT-hook 1-G6PD (FOXM1-HMGA1-G6PD) transcriptional regulatory pathway, in which TGFβ1 inhibited the ubiquitination and degradation of FOXM1 protein. Additionally, HMGA1 induced TGFβ1 expression, and neutralized TGFβ1 in the culture medium downregulated HMGA1 levels, suggesting the existence of a TGFβ1-FOXM1-HMGA1-TGFβ1 positive feedback loop and its role in maintaining G6PD expression. Further investigations showed that exogenous TGFβ1 enhanced the cisplatin resistance of NSCLC cells, while disrupting the FOXM1-HMGA1-G6PD pathway, thereby sensitizing the cells to cisplatin. Consistently, the TGFβ1-FOXM1-HMGA1-G6PD axis was confirmed in NSCLC tissues, and overactivation of this axis predicted poor survival in NSCLC patients. Collectively, the results of this study demonstrate that the TGFβ1-FOXM1-HMGA1-TGFβ1 positive feedback loop plays a crucial role in the cisplatin resistance of NSCLC by upregulating the expression of G6PD, providing a potential therapeutic target to restore chemosensitivity in cisplatin-resistant NSCLC.
Indexed as
Identifiers
31814893PMC6895501W2997580289What OpenQuestion holds
Registered trials
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.