Adrenergic signaling promotes the expansion of cancer stem-like cells of malignant peripheral nerve sheath tumors
Adrenergic signaling promotes the expansion of cancer stem-like cells of malignant peripheral nerve sheath tumors
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DOI：
10.1016/j.bbrc.2021.03.172
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发表时间：
2021-04-16
影响因子：
3.1
通讯作者：
Kamiya, Atsunori
中科院分区：
文献类型：
--
作者：
Huang, Rongsheng;Fujimura, Atsushi;Kamiya, Atsunori
恶性周围神经鞘瘤（MPNST）是一种发生于周围神经组织的高度恶性肿瘤，已知其对放射和化学疗法具有高度抗性。虽然有几个报告的基因突变和表观遗传变化，定义的发病机制MPNST，有足够的信息，有助于恶性MPNST的微环境。在本研究中，我们证明肾上腺素增加MPNST中的癌症干细胞数量。该效应由肾上腺素刺激β-2肾上腺素能受体（ADRB 2）介导，后者激活Hippo转换器雅普/TAZ。抑制和RNAi实验表明，抑制ADRB 2减弱肾上腺素触发的雅普/TAZ的活性，随后减弱MPNST细胞的干细胞性。MPNST患者标本中ADRB 2-雅普/TAZ轴也得到证实。ADRB 2水平高的患者预后明显较差。这些数据表明，肾上腺素恶化MPNST的预后，并可能有助于MPNST的新的治疗策略的发展。(c)2021年，任作家。爱思唯尔公司出版这是一个在CC BY-NC-ND许可证下的开放获取文章（http：//creativecommons.org/licenses/by-nc-nd/4.0/）。
Malignant peripheral nerve sheath tumor (MPNST), a highly malignant tumor that arises in peripheral nerve tissues, is known to be highly resistant to radiation and chemotherapy. Although there are several reports on genetic mutations and epigenetic changes that define the pathogenesis of MPNST, there is insufficient information regarding the microenvironment that contributes to the malignancy of MPNST. In the present study, we demonstrate that adrenaline increases the cancer stem cell population in MPNST. This effect is mediated by adrenaline stimulation of beta-2 adrenergic receptor (ADRB2), which activates the Hippo transducer, YAP/TAZ. Inhibition and RNAi experiments revealed that inhibition of ADRB2 attenuated the adrenaline-triggered activity of YAP/TAZ and subsequently attenuated MPNST cells stemness. Furthermore, ADRB2-YAP/TAZ axis was confirmed in the MPNST patients' specimens. The prognosis of patients with high levels of ADRB2 was found to be significantly worse. These data show that adrenaline exacerbates MPNST prognosis and may aid the development of new treatment strategies for MPNST.(c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).