Role of Merlin/NF2 inactivation in tumor biology.
Role of Merlin/NF2 inactivation in tumor biology.
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DOI：
10.1038/onc.2015.125
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发表时间：
2016-02-04
期刊：
影响因子：
8
通讯作者：
Fernández-Valle C
中科院分区：
文献类型：
--
作者：
Petrilli AM;Fernández-Valle C
Merlin（Moesin-ezrin-radixin-like protein，也称为Schwannomin）是一种由神经纤维瘤病2型基因NF 2编码的肿瘤抑制蛋白。NF 2中的功能缺失突变或缺失导致神经纤维瘤病2型（NF 2），一种神经系统的多发性肿瘤形成疾病。NF 2的特点是发展为双侧前庭神经鞘瘤。患有NF 2的患者也可以在其他颅神经和周围神经上发展神经鞘瘤，以及脑膜瘤和室管膜瘤。唯一可能的治疗方法是手术/放射外科手术，这通常会导致相关神经功能丧失。目前迫切需要减缓或消除肿瘤并防止其在NF 2患者中形成的化疗。有趣的是，NF 2突变和merlin失活也发生在自发性神经鞘瘤和脑膜瘤以及其他类型的癌症中，包括间皮瘤、多形性胶质瘤、乳腺癌、结直肠癌、皮肤癌、透明细胞肾细胞癌、肝癌和前列腺癌。除恶性间皮瘤外，NF 2突变或失活在癌症中的作用尚未受到太多关注，NF 2可能与预后和未来的化疗方法有关。这篇综述讨论了梅林功能丧失对NF 2相关肿瘤和常见人类癌症的影响。我们还讨论了NF 2基因状态和merlin信号通路在不同肿瘤类型中的影响，以及导致肿瘤发生、进展和药物耐药的分子机制。
Merlin ((Moesin-ezrin-radixin-like protein, also known as schwannomin) is a tumor suppressor protein encoded by the neurofibromatosis type 2 gene NF2. Loss of function mutations or deletions in NF2 cause Neurofibromatosis type 2 (NF2), a multiple tumor forming disease of the nervous system. NF2 is characterized by the development of bilateral vestibular schwannomas. Patients with NF2 can also develop schwannomas on other cranial and peripheral nerves, as well as meningiomas and ependymomas. The only potential treatment is surgery/radiosurgery which often results in loss of function of the involved nerve. There is an urgent need for chemotherapies that slow or eliminate tumors and prevent their formation in NF2 patients. Interestingly NF2 mutations and merlin inactivation also occur in spontaneous schwannomas and meningiomas, as well as other types of cancer including mesothelioma, glioma multiforme, breast, colorectal, skin, clear cell renal cell carcinoma, hepatic and prostate cancer. Except for malignant mesotheliomas, the role of NF2 mutation or inactivation has not received much attention in cancer, and NF2 might be relevant for prognosis and future chemotherapeutic approaches. This review discusses the influence of merlin loss of function in NF2-related tumors and common human cancers. We additionally discuss the NF2 gene status and merlin signaling pathways affected in the different tumor types and the molecular mechanisms that lead to tumorigenesis, progression and pharmacological resistance.