Bone morphogenetic protein receptor 1α promotes osteolytic lesion of oral squamous cell carcinoma by SHH-dependent osteoclastogenesis.
Bone morphogenetic protein receptor 1α promotes osteolytic lesion of oral squamous cell carcinoma by SHH-dependent osteoclastogenesis.
复制标题
BMPR1α 通过 SHH 依赖性破骨细胞生成促进口腔鳞状细胞癌的溶骨性病变
作者：
口腔鳞状细胞癌是一种侵袭性强的肿瘤，通常侵犯上颌骨或下颌骨。口腔鳞癌对下颌骨的侵犯程度和方式是决定治疗方案和患者预后的重要因素。然而，下颌骨侵犯的过程尚未完全了解。以下研究通过关注骨形态发生蛋白受体1α（BMPR1α）和Sonic hedgehog（SHH）信号来探讨调节OSCC下颌骨侵袭的分子机制。BMPR1α与OSCC患者骨缺损呈正相关。BMPR1α信号通过OSCC细胞与破骨细胞祖细胞的相互作用调节破骨细胞的分化和吸收活性，这一过程由肿瘤细胞分泌的SHH介导。SHH的抑制可以保护骨骼免受肿瘤诱导的溶骨活性的影响。这些结果提供了一个潜在的新的治疗策略，以控制口腔鳞癌侵入颌骨。在口腔鳞状细胞癌（OSCC）组织中，骨形态发生蛋白受体1α的过表达激活了下游信号通路，诱导转录因子Smad4调控的Sonic hedgehog（SHH）的表达。SHH以旁分泌方式促进破骨细胞的分化和骨吸收活性，促进OSCC引起的骨结合缺损。
Oral squamous cell carcinoma (OSCC) is an aggressive tumor that usually invades the maxilla or mandible. The extent and pattern of mandibular bone invasion caused by OSCC are the most important factors determining the treatment plan and patients' prognosis. Yet, the process of mandibular invasion is not fully understood. The following study explores the molecular mechanism that regulates the mandibular invasion of OSCC by focusing on bone morphogenetic protein receptor 1α (BMPR1α) and Sonic hedgehog (SHH) signals. We found that BMPR1α was positively correlated to bone defect of OSCC patients. Mechanistically, BMPR1α signaling regulated the differentiation and resorption activity of osteoclasts through the interaction of OSCC cells and osteoclast progenitors, and this process was mediated by SHH secreted by tumor cells. The inhibition of SHH protected bone from tumor‐induced osteolytic activity. These results provide a potential new treatment strategy for controlling OSCC from invading the jawbones. In oral squamous cell carcinoma (OSCC) tissues, overexpression of bone morphogenetic protein receptor 1α activates the downstream signaling and induces the expression of Sonic hedgehog (SHH) regulated by transcript factor Smad4. SHH enhances osteoclasts' differentiation and resorption activity in a paracrine way, promoting the bond defect induced by OSCC.
登录
查看更多内容
DOI：
10.1016/j.revsto.2016.06.004
发表时间：
2016-11-01
影响因子：
--
作者：
Farrow, E. S.;Boulanger, T.;Julieron, M.
通讯作者：
Julieron, M.
DOI：
10.1016/j.bjoms.2012.01.010
发表时间：
2012-12-01
影响因子：
1.8
作者：
Laraway, D. C.;Lakshmiah, R.;Rogers, S. N.
通讯作者：
Rogers, S. N.
影响因子：
16.6
作者：
Gooding, Sarah;Olechnowicz, Sam W. Z.;Edwards, Claire M.
通讯作者：
Edwards, Claire M.
间充质 Sufu 通过 Shh 信号调节下颌磨牙的发育
影响因子：
7.6
作者：
Li, J.;Xu, J.;Zhang, Z.
通讯作者：
Zhang, Z.
影响因子：
7.5
作者：
Alarmo, Emma-Leena;Huhtala, Heini;Kallioniemi, Anne
通讯作者：
Kallioniemi, Anne