Integrin α1 upregulation by TF:FVIIa complex promotes cervical cancer migration through PAR2-dependent MEK1/2 activation.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE
    • Publication Information:
      Publication: <2002- >: San Diego, CA : Elsevier
      Original Publication: New York, Academic Press.
    • Subject Terms:
      Receptor, PAR-2*/metabolism ; Receptor, PAR-2*/genetics ; Cell Movement* ; Uterine Cervical Neoplasms*/metabolism ; Uterine Cervical Neoplasms*/pathology ; Uterine Cervical Neoplasms*/genetics ; Factor VIIa*/metabolism ; Up-Regulation* ; Thromboplastin*/metabolism ; Thromboplastin*/genetics ; MAP Kinase Kinase 1*/metabolism ; MAP Kinase Kinase 1*/genetics; Humans ; Female ; MAP Kinase Kinase 2/metabolism ; MAP Kinase Kinase 2/genetics ; Gene Expression Regulation, Neoplastic ; HeLa Cells ; Cell Line, Tumor ; Enzyme Activation
    • Abstract:
      Tissue factor (TF) and protease-activated receptor 2 (PAR2) have been associated with the progression of cancer, while integrins are essential for the adhesion and migration of cancer cells. This study aimed to explore the cross-talk between the TF:FVIIa complex, PAR2 signaling, and the expression of integrin α1 in cervical cancer cells. Utilizing data from The Cancer Genome Atlas (TCGA), the research examined the relationship between the TF and PAR2 genes and the integrin α1 gene (ITGA1) in reproductive cancers, revealing a positive correlation between integrin α1 expression and both TF and PAR2 genes. Analyses through Western blotting and RT-PCR demonstrated that TF:FVIIa complex transactivates PAR2, which significantly increases the phosphorylation of MEK1/2 and subsequently elevates integrin α1 expression. Inhibition of either PAR2 or MEK1/2 resulted in a decrease in the FVIIa-induced increase in integrin α1 expression. Additionally, cell migration studies indicated that elevated expression of integrin α1, mediated by the TF:FVIIa/PAR2 pathway, was linked to enhanced cell migration, which could be inhibited by blocking integrin α1. This investigation uncovers a novel signaling pathway in HeLa cells, highlighting the significance of the TF:FVIIa:PAR2 axis in modulating integrins that are vital for cancer progression, thereby offering insights for potential targeted therapeutic approaches in cancer treatment.
      Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Paranitharan Nagarajan reports financial support was provided by Council of Scientific & Industrial Research (CSIR). Velayuthaprabhu Shanmugam reports financial support was provided by Rashtriya Uchchatar Shiksha Abhiyan (RUSA 2.0 BEICH). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: Cell migration; Cervical cancer; Integrin; PAR2; Tissue factor
    • Accession Number:
      0 (Receptor, PAR-2)
      EC 3.4.21.21 (Factor VIIa)
      9035-58-9 (Thromboplastin)
      EC 2.7.12.2 (MAP Kinase Kinase 1)
      EC 2.7.12.2 (MAP Kinase Kinase 2)
      EC 2.7.12.2 (MAP2K1 protein, human)
      EC 2.7.1.- (MAP2K2 protein, human)
      0 (F2RL1 protein, human)
    • Publication Date:
      Date Created: 20241210 Date Completed: 20241219 Latest Revision: 20241219
    • Publication Date:
      20241220
    • Accession Number:
      10.1016/j.bbrc.2024.151151
    • Accession Number:
      39657349