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PTHrP promotes malignancy of human oral cancer cell downstream of the EGFR signaling
Title: | PTHrP promotes malignancy of human oral cancer cell downstream of the EGFR signaling |
Authors: | Yamada, Tamaki Browse this author | Tsuda, Masumi Browse this author →KAKEN DB | Ohba, Yusuke Browse this author →KAKEN DB | Kawaguchi, Hideaki Browse this author →KAKEN DB | Totsuka, Yasunori Browse this author →KAKEN DB | Shindoh, Masanobu Browse this author →KAKEN DB |
Keywords: | PTHrP | EGFR | AG1478 | RNA interference | Oral cancer | Therapeutics |
Issue Date: | 11-Apr-2008 |
Publisher: | Elsevier |
Journal Title: | Biochemical and Biophysical Research Communications |
Volume: | 368 |
Issue: | 3 |
Start Page: | 575 |
End Page: | 581 |
Publisher DOI: | 10.1016/j.bbrc.2008.01.121 |
PMID: | 18261460 |
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. |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/54567 |
Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 大場 雄介
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