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Osteopontin isoform c promotes the survival of cisplatin-treated NSCLC cells involving NFATc2-mediated suppression on calcium-induced ROS levels.

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  • معلومة اضافية
    • المصدر:
      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
    • بيانات النشر:
      Original Publication: London : BioMed Central, [2001-
    • الموضوع:
      Calcium/*adverse effects ; Carcinoma, Non-Small-Cell Lung/*drug therapy ; Carcinoma, Non-Small-Cell Lung/*genetics ; Lung Neoplasms/*drug therapy ; Lung Neoplasms/*genetics ; NFATC Transcription Factors/*metabolism ; Osteopontin/*genetics ; Protein Isoforms/*metabolism ; Reactive Oxygen Species/*metabolism; Apoptosis ; Carcinoma, Non-Small-Cell Lung/mortality ; Carcinoma, Non-Small-Cell Lung/pathology ; Female ; Humans ; Lung Neoplasms/mortality ; Lung Neoplasms/pathology ; Male ; Transfection ; Tumor Microenvironment
    • نبذة مختصرة :
      Background: Tumor microenvironment (TME) critically contributed to the malignant progression of transformed cells and the chemical responses to chemotherapy reagents. Osteopontin (OPN) is a secretory onco-protein with several splicing isoforms, all of which were known to regulate tumor growth and able to alter cell-cell or cell-TME communication, however, the exact role and regulation of the OPN splicing isoforms was not well understood.
      Methods: In this study, the effects of conditioned medium from the culture of OPN splicing isoforms overexpressing cells on cell functions were evaluated. The methods of nuclear calcium reporter assays and subcellular distribution of nuclear factor of activated T cells c2 (NFATc2) assays were used to investigate the molecular mechanism underlining the roles of OPN splicing isoforms.
      Results: We found that the survival of NSCLC cells treated with cisplatin was increased by secretory OPNc in the condition medium, where reduction of apoptosis by OPNc was associated with the activation of cellular calcium signals and subsequent nuclear translocation of NFATc2.
      Conclusions: The results revealed a mechanism of OPN and downstream signal for tumor cells to survive in chemo-stressed TME, which emphasized the importance of secretory proteins in alternative splicing isoforms. Our study not only demonstrated the importance of OPN neutralization for anti-tumor effects, but also implied that modulation in calcium/NFATc2/ROS axis could be a novel approach for improving the long-term outcome of NSCLC treatment.
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    • Contributed Indexing:
      Keywords: NFATc2; Osteopontin; Reactive oxygen species; Splicing isoform; Tumor microenvironment
    • الرقم المعرف:
      0 (NFATC Transcription Factors)
      0 (NFATC2 protein, human)
      0 (Protein Isoforms)
      0 (Reactive Oxygen Species)
      106441-73-0 (Osteopontin)
      SY7Q814VUP (Calcium)
    • الموضوع:
      Date Created: 20210630 Date Completed: 20211019 Latest Revision: 20211019
    • الموضوع:
      20250114
    • الرقم المعرف:
      PMC8243455
    • الرقم المعرف:
      10.1186/s12885-021-08495-z
    • الرقم المعرف:
      34187410