ArticleCell death & disease2019
PFKFB3 inhibition reprograms malignant pleural mesothelioma to nutrient stress-induced macropinocytosis and ER stress as independent binary adaptive responses.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 44 citations in OpenAlex.
- Nuclear cathepsin L induces DNA damage by regulating DNA repair factors in ovarian cancer.Oncogene · 2026Article
- Metabolic vulnerabilities in pleural mesothelioma.Oncogenesis · 2026Review
- Beyond the Vasculature: The Emerging Role of Systemic Metabolism and Immunometabolism in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2026Review
- Cellular Regulation of Macropinocytosis.International journal of molecular sciences · 2024Review
- Targeting the Warburg effect: A revisited perspective from molecular mechanisms to traditional and innovative therapeutic strategies in cancer.Acta pharmaceutica Sinica. B · 2024Review
- Small molecule inhibitors for cancer metabolism: promising prospects to be explored.Journal of cancer research and clinical oncology · 2023Review
- Inhibition of Macropinocytosis Enhances the Sensitivity of Osteosarcoma Cells to Benzethonium Chloride.Cancers · 2023Article
- The role of PFKFB3 in maintaining colorectal cancer cell proliferation and stemness.Molecular biology reports · 2022Review
- PFKFB3 works on the FAK-STAT3-SOX2 axis to regulate the stemness in MPM.British journal of cancer · 2022Article
- A miR-34a-guided, tRNACell death discovery · 2022Article
- PFKFB3 regulates cancer stemness through the hippo pathway in small cell lung carcinoma.Oncogene · 2022Article
- Targeting LRRC15 Inhibits Metastatic Dissemination of Ovarian Cancer.Cancer research · 2022Article
- PFKFB3 Regulates Chemoresistance, Metastasis and StemnessFrontiers in oncology · 2022Article
- Exploiting cancer's drinking problem: regulation and therapeutic potential of macropinocytosis.Trends in cancer · 2022Review
- Silencing of PFKFB3 protects podocytes against high glucose‑induced injury by inducing autophagy.Molecular medicine reports · 2021Article
- Review
- Biological basis for novel mesothelioma therapies.British journal of cancer · 2021Review
- Targeting MYC-enhanced glycolysis for the treatment of small cell lung cancer.Cancer & metabolism · 2021Article
- Article
- Group III phospholipase A2 downregulation attenuated survival and metastasis in ovarian cancer and promotes chemo-sensitization.Journal of experimental & clinical cancer research : CR · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The metabolic signatures of cancer cells are often associated with elevated glycolysis. Pharmacological (PFK158 treatment) and genetic inhibition of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a critical control point in the glycolytic pathway, decreases glucose uptake, ATP production, and lactate dehydrogenase activity and arrests malignant pleural mesothelioma (MPM) cells in the G0/G1 phase to induce cell death. To overcome this nutrient stress, inhibition of PFKFB3 activity led to an escalation in endoplasmic reticulum (ER) activity and aggravated ER stress mostly by upregulating BiP and GADD153 expression and activation of the endocytic Rac1-Rab5-Rab7 pathway resulting in a unique form of cell death called "methuosis" in both the sarcomatoid (H28) and epithelioid (EMMeso) cells. Transmission electron microscopy (TEM) analysis showed the formation of nascent macropinocytotic vesicles, which rapidly coalesced to form large vacuoles with compromised lysosomal function. Both immunofluorescence microscopy and co-immunoprecipitation analyses revealed that upon PFKFB3 inhibition, two crucial biomolecules of each pathway, Rac1 and Calnexin interact with each other. Finally, PFK158 alone and in combination with carboplatin-inhibited tumorigenesis of EMMeso xenografts in vivo. Since most cancer cells exhibit an increased glycolytic rate, these results provide evidence for PFK158, in combination with standard chemotherapy, may have a potential in the treatment of MPM.
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.