ArticleBMC cancer2021
TGF-β protects osteosarcoma cells from chemotherapeutic cytotoxicity in a SDH/HIF1α dependent manner.
Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Article
- Osteosarcoma as a communication-driven disease: redefining tumor-bone signaling networks as therapeutic targets.Frontiers in oncology · 2026Review
- Molecular Crosstalk Between RUNX2 and HIF-1α in Osteosarcoma: Implications for Angiogenesis, Metastasis, and Therapy Resistance.International journal of molecular sciences · 2025Review
- Microenvironment matters: insights from the FOSTER consortium on microenvironment-driven approaches to osteosarcoma therapy.Cancer metastasis reviews · 2025Review
- The Role of Epithelial-Mesenchymal Transition in Osteosarcoma Progression: From Biology to Therapy.Diagnostics (Basel, Switzerland) · 2025Review
- The malignant dialogue between cancer-associated fibroblasts and osteosarcoma cells: microenvironment-mediated drug resistance and therapeutic targets.Frontiers in immunology · 2025Review
- Modulation of Chemotherapy Sensitivity of Breast Cancer Cells through Transforming Growth Factor-beta Pathway-mediated Alterations in DNA Damage Response.International journal of medical sciences · 2025Article
- Tricarboxylic Acid Cycle Relationships with Non-Metabolic Processes: A Short Story with DNA Repair and Its Consequences on Cancer Therapy Resistance.International journal of molecular sciences · 2024Review
- Inactivation of adenosine receptor 2A suppresses endothelial-to-mesenchymal transition and inhibits subretinal fibrosis in mice.Science translational medicine · 2024Article
- Reprogramming of glucose metabolism: Metabolic alterations in the progression of osteosarcoma.Journal of bone oncology · 2024Review
- Hypoxia inducible factor-1ɑ as a potential therapeutic target for osteosarcoma metastasis.Frontiers in pharmacology · 2024Review
- Article
- Metabolic reprogramming in osteosarcoma.Pediatric discovery · 2023Review
- Deciphering the Signaling Mechanisms of Osteosarcoma Tumorigenesis.International journal of molecular sciences · 2023Review
- The roles of glycolysis in osteosarcoma.Frontiers in pharmacology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn the widespread adoption of chemotherapy, drug resistance has been the major obstacle to tumor elimination in cancer patients. Our aim was to explore the role of TGF-β in osteosarcoma-associated chemoresistance.
methodsWe performed a cytotoxicity analysis of methotrexate (MTX) and cisplatin (CIS) in TGF-β-treated osteosarcoma cells. Then, the metabolite profile of the core metabolic energy pathways in Saos-2 and MG-63 cell extracts was analyzed by
resultsThe metabolic analysis revealed enhanced succinate production in osteosarcoma cells after TGF-β treatment. We further found a decrease in SDH expression and an increase in HIF1α expression in TGF-β-treated osteosarcoma cells. Consistently, blockade of SDH efficiently enhanced the resistance of Saos-2 and MG-63 cells to MTX and CIS. Additionally, a HIF1α inhibitor significantly strengthened the anticancer efficacy of the chemotherapeutic drugs in mice with osteosarcoma cancer.
conclusionOur study demonstrated that TGF-β attenuated the expression of SDH by reducing the transcription factor STAT1. The reduction in SDH then caused the upregulation of HIF1α, thereby rerouting glucose metabolism and aggravating chemoresistance in osteosarcoma cells. Linking tumor cell metabolism to the formation of chemotherapy resistance, our study may guide the development of additional treatments for osteosarcoma.
Indexed as
Identifiers
What 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.