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Title
  • en PTHrP promotes malignancy of human oral cancer cell downstream of the EGFR signaling
Creator
Accessrights open access
Subject
  • Other en PTHrP
  • Other en EGFR
  • Other en AG1478
  • Other en RNA interference
  • Other en Oral cancer
  • Other en Therapeutics
  • NDC 490
Description
  • Abstract en Parathyroid hormone-related protein (PTHrP) is detected in many aggressive tumors and involved in malignant conversion; however, the underlying mechanism remains obscure. Here, we identified PTHrP as a mediator of epidermal growth factor receptor (EGFR) signaling to promote the malignancies of oral cancers. PTHrP mRNA was abundantly expressed in most of the quiescent oral cancer cells, and was significantly upregulated by EGF stimulation via ERK and p38 MAPK. PTHrP silencing by RNA interference, as well as EGFR inhibitor AG1478 treatment, significantly suppressed cell proliferation, migration, and invasiveness. Furthermore, combined treatment of AG1478 and PTHrP knockdown achieved synergistic inhibition of malignant phenotypes. Recombinant PTHrP substantially promoted cell motility, and rescued the inhibition by PTHrP knockdown, suggesting the paracrine/autocrine function of PTHrP. These data indicate that PTHrP contributes to the malignancy of oral cancers downstream of EGFR signaling, and may thus provide a therapeutic target for oral cancer.
Publisher en Elsevier
Date
    Issued2008-04-11
Language
  • eng
Resource Type journal article
Version Type AM
Identifier HDL http://hdl.handle.net/2115/54567
Relation
  • isVersionOf DOI https://doi.org/10.1016/j.bbrc.2008.01.121
  • PMID 18261460
Journal
    • PISSN 0006-291X
    • NCID AA00564395
      • en Biochemical and Biophysical Research Communications
      • Volume Number368 Issue Number3 Page Start575 Page End581
File
Oaidate 2023-07-26