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PTHrP promotes malignancy of human oral cancer cell downstream of the EGFR signaling

Biochem Biophys Res Commun_368(3)_575-581.pdf1.9 MBPDF見る/開く

タイトル: PTHrP promotes malignancy of human oral cancer cell downstream of the EGFR signaling
著者: Yamada, Tamaki 著作を一覧する
Tsuda, Masumi 著作を一覧する
Ohba, Yusuke 著作を一覧する
Kawaguchi, Hideaki 著作を一覧する
Totsuka, Yasunori 著作を一覧する
Shindoh, Masanobu 著作を一覧する
キーワード: PTHrP
RNA interference
Oral cancer
発行日: 2008年 4月11日
出版者: Elsevier
誌名: Biochemical and Biophysical Research Communications
巻: 368
号: 3
開始ページ: 575
終了ページ: 581
出版社 DOI: 10.1016/j.bbrc.2008.01.121
抄録: 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.
資料タイプ: article (author version)
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 大場 雄介


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