ArticleNeoplasia (New York, N.Y.)2008
Plasminogen activator inhibitor 1 protects fibrosarcoma cells from etoposide-induced apoptosis through activation of the PI3K/Akt cell survival pathway.
Article in Neoplasia (New York, N.Y.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 48 citations in OpenAlex.
- Targeting autophagy and plasminogen activator inhibitor-1 increases survival and remodels the tumor microenvironment in glioblastoma.Journal of experimental & clinical cancer research : CR · 2025Article
- The development of radioresistant oral squamous carcinoma cell lines and identification of radiotherapy-related biomarkers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Article
- Coculture of cancer cells with platelets increases their survival and metastasis by activating the TGFβ/Smad/PAI-1 and PI3K/AKT pathways.International journal of biological sciences · 2023Article
- Cancer-Associated Fibroblasts: Mechanisms of Tumor Progression and Novel Therapeutic Targets.Cancers · 2022Review
- Sustained postoperative plasma elevations of plasminogen activator inhibitor-1 following minimally invasive colorectal cancer resection.Molecular and clinical oncology · 2022Article
- SOX2-OT induced by PAI-1 promotes triple-negative breast cancer cells metastasis by sponging miR-942-5p and activating PI3K/Akt signaling.Cellular and molecular life sciences : CMLS · 2022Article
- Human amniotic mesenchymal stem cells and their paracrine factors promote wound healing by inhibiting heat stress-induced skin cell apoptosis and enhancing their proliferation through activating PI3K/AKT signaling pathway.Stem cell research & therapy · 2019Article
- Tumor-secreted PAI-1 promotes breast cancer metastasis via the induction of adipocyte-derived collagen remodeling.Cell communication and signaling : CCS · 2019Article
- Inhibition of PAI-1 limits chemotherapy resistance in lung cancer through suppressing myofibroblast characteristics of cancer-associated fibroblasts.Journal of cellular and molecular medicine · 2019Article
- LDR-Induced miR-30a and miR-30b Target the PAI-1 Pathway to Control Adverse Effects of NSCLC Radiotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- miR-34a exerts as a key regulator in the dedifferentiation of osteosarcoma via PAI-1-Sox2 axis.Cell death & disease · 2018Article
- SerpinE2, a poor biomarker of endometrial cancer, promotes the proliferation and mobility of EC cells.Cancer biomarkers : section A of Disease markers · 2017Article
- uPA/uPAR and SERPINE1 in head and neck cancer: role in tumor resistance, metastasis, prognosis and therapy.Oncotarget · 2016Review
- Plasminogen activator inhibitor-1 enhances radioresistance and aggressiveness of non-small cell lung cancer cells.Oncotarget · 2016Article
- Article
- Plasminogen Activator Inhibitor-1 in Cancer: Rationale and Insight for Future Therapeutic Testing.Cancer research · 2015Review
- Plasminogen activator inhibitor-1 is increased in colonic epithelial cells from patients with colitis-associated cancer.Journal of Crohn's & colitis · 2013Article
- Protumorigenic activity of plasminogen activator inhibitor-1 through an antiapoptotic function.Journal of the National Cancer Institute · 2012Article
- siRNA against plasminogen activator inhibitor-1 ameliorates bleomycin-induced lung fibrosis in rats.Acta pharmacologica Sinica · 2012Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High levels of plasminogen activator inhibitor (PAI-1) in tumors are associated with poor prognosis in several cancer types, and the reason for this association is not fully understood. Plasminogen activator inhibitor 1 has been suggested to contribute to tumor growth by protecting cancer cells from apoptosis, and we have previously shown that wild type murine fibrosarcoma cells are significantly more resistant to apoptosis induced by chemotherapy than PAI-1-deficient fibrosarcoma cells. Here, we further investigated the molecular mechanisms underlying the antiapoptotic function of PAI-1 focusing on the phosphatidylinositol 3-phosphate kinase (PI3K)/Akt cell survival pathway. We demonstrate that the activation level of the Akt cell survival pathway is reduced in PAI-1-deficient cells. Inhibition of either PI3K or Akt by synthetic inhibitors sensitized the wild type but not the PAI-1-deficient cells to etoposide-induced cell death. More importantly, reintroduction of PAI-1 expression in PAI-1-deficient cells induced an increase in Akt activity and protection against etoposide-induced apoptosis. Concordantly, silencing of PAI-1 by RNA interference in wild type fibrosarcoma cells decreased the level of active Akt, and this was accompanied by a sensitization of the cells to etoposide-induced cell death. Altogether, our data suggest that PAI-1 influences sensitivity to etoposide-induced apoptosis through the PI3K/Akt cell survival pathway by acting upstream of PI3K and Akt. This points to PAI-1 as a possible therapeutic target in cancer diseases where PAI-1 inhibits chemotherapy-induced apoptosis.
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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.