دورية أكاديمية
أعرض في EDS

The peroxidase PRDX1 inhibits the activated phenotype in mammary fibroblasts through regulating c-Jun N-terminal kinases.

التفاصيل البيبلوغرافية
العنوان: The peroxidase PRDX1 inhibits the activated phenotype in mammary fibroblasts through regulating c-Jun N-terminal kinases.
المؤلفون: Jezierska-Drutel A; Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.; Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, 29425, USA., Attaran S; Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.; Women's Cancer Research Center, UPMC Hillman Cancer Center, Pittsburgh, PA, 15213, USA., Hopkins BL; Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, 15213, USA.; Women's Cancer Research Center, UPMC Hillman Cancer Center, Pittsburgh, PA, 15213, USA., Skoko JJ; Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.; Women's Cancer Research Center, UPMC Hillman Cancer Center, Pittsburgh, PA, 15213, USA., Rosenzweig SA; Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, 29425, USA., Neumann CA; Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA, 15213, USA. neumannc@upmc.edu.; Women's Cancer Research Center, UPMC Hillman Cancer Center, Pittsburgh, PA, 15213, USA. neumannc@upmc.edu.
المصدر: BMC cancer [BMC Cancer] 2019 Aug 16; Vol. 19 (1), pp. 812. Date of Electronic Publication: 2019 Aug 16.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 100967800 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2407 (Electronic) Linking ISSN: 14712407 NLM ISO Abbreviation: BMC Cancer Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central, [2001-
مواضيع طبية MeSH: Phenotype*, Fibroblasts/*metabolism , Mammary Glands, Animal/*cytology , Mitogen-Activated Protein Kinase 8/*metabolism , Peroxiredoxins/*genetics , Peroxiredoxins/*metabolism, Actins/metabolism ; Animals ; Anthracenes/pharmacology ; Female ; Gene Knockout Techniques ; HEK293 Cells ; Humans ; Hydrogen Peroxide/metabolism ; Mice ; Mice, Inbred BALB C ; Mitogen-Activated Protein Kinase 8/antagonists & inhibitors ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; Transfection ; Tumor Microenvironment
مستخلص: Background: Reactive oxygen species (ROS), including hydrogen peroxide, drive differentiation of normal fibroblasts into activated fibroblasts, which can generate high amounts of hydrogen peroxide themselves, thereby increasing oxidative stress in the microenvironment. This way, activated fibroblasts can transition into cancer-associated fibroblasts (CAFs).
Methods: Mammary fibroblasts from either female 8 weeks old PRDX1 knockout and wildtype mice or Balb/c mice were studied for characteristic protein expression using immunofluorescence and immunoblotting. Cancer-associated fibroblasts was examined by transwell migration and invasion assays. The binding of PRDX1 to JNK1 was assessed by co-immuneprecipitation and JNK regulation of CAF phenotypes was examined using the JNK inhibitor SP600125. Extracellular hydrogen peroxide levels were measured by chemiluminescence via the reaction between hypochlorite and luminol. Statistical analyses were done using Students t-test.
Results: We show here PRDX1 activity as an essential switch in regulating the activated phenotype as loss of PRDX1 results in the development of a CAF-like phenotype in mammary fibroblasts. We also show that PRDX1 regulates JNK kinase signaling thereby inhibiting CAF-like markers and CAF invasion. Inhibition of JNK activity reduced these behaviors.
Conclusions: These data suggest that PRDX1 repressed the activated phenotype of fibroblasts in part through JNK inhibition which may present a novel therapeutic option for CAF-enriched cancers such as breast cancer.
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معلومات مُعتمدة: P30 CA047904 United States CA NCI NIH HHS; R01 CA131350 United States CA NCI NIH HHS; P30CA047904 United States CA NCI NIH HHS; R01 CA078887 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Breast cancer; Breast tumorigenesis; Cancer-associated fibroblasts; Hydrogen peroxide; JNK; Mammary fibroblasts; peroxiredoxin1
المشرفين على المادة: 0 (Actins)
0 (Anthracenes)
0 (Reactive Oxygen Species)
0 (alpha-smooth muscle actin, mouse)
1TW30Y2766 (pyrazolanthrone)
BBX060AN9V (Hydrogen Peroxide)
EC 1.11.1.15 (PRDX1 protein, human)
EC 1.11.1.15 (Peroxiredoxins)
EC 1.11.1.15 (Prdx1 protein, mouse)
EC 2.7.11.24 (Mitogen-Activated Protein Kinase 8)
تواريخ الأحداث: Date Created: 20190818 Date Completed: 20200225 Latest Revision: 20221221
رمز التحديث: 20221221
مُعرف محوري في PubMed: PMC6697950
DOI: 10.1186/s12885-019-6031-4
PMID: 31419957
قاعدة البيانات: MEDLINE
الوصف
تدمد:1471-2407
DOI:10.1186/s12885-019-6031-4