Abstract:
: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.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Yamada T,Tsuda M,Ohba Y,Kawaguchi H,Totsuka Y,Shindoh Mdoi
10.1016/j.bbrc.2008.01.121subject
Has Abstractpub_date
2008-04-11 00:00:00pages
575-81issue
3eissn
0006-291Xissn
1090-2104pii
S0006-291X(08)00169-1journal_volume
368pub_type
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journal_title:Biochemical and biophysical research communications
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journal_title:Biochemical and biophysical research communications
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journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
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