PTHrP promotes malignancy of human oral cancer cell downstream of the EGFR signaling
PTHrP promotes malignancy of human oral cancer cell downstream of the EGFR signaling
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DOI：
10.1016/j.bbrc.2008.01.121
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发表时间：
2008-04-11
影响因子：
3.1
通讯作者：
Shindoh, Masanobu
中科院分区：
文献类型：
--
作者：
Yamada, Tamaki;Tsuda, Masumi;Shindoh, Masanobu
甲状旁腺相关蛋白（PTHrP）在许多侵袭性肿瘤中被检测到，并参与恶性转化;然而，其潜在机制仍不清楚。在这里，我们确定PTHrP作为介导的表皮生长因子受体（EGFR）信号，以促进口腔癌的恶性。PTHrP mRNA在大多数静止期口腔癌细胞中大量表达，并通过ERK和p38 MAPK被EGF刺激显著上调。PTHrP沉默RNA干扰，以及EGFR抑制剂AG 1478治疗，显着抑制细胞增殖，迁移和侵袭。此外，AG 1478和PTHrP敲低的组合治疗实现了恶性表型的协同抑制。重组PTHrP显著促进细胞运动，并通过PTHrP敲低解除抑制，提示PTHrP的旁分泌/自分泌功能。这些数据表明，PTHrP有助于口腔癌的恶性肿瘤下游的EGFR信号传导，并因此可能提供一个治疗目标的口腔癌。(c)2008年爱思唯尔公司All rights reserved.
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. (c) 2008 Elsevier Inc. All rights reserved.