The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, PR China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, PR China.
The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, PR China; Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, Guangdong, PR China.
Biochim Biophys Acta Rev Cancer. 2020 Dec;1874(2):188435. doi: 10.1016/j.bbcan.2020.188435. Epub 2020 Sep 22.
Lysyl oxidase-like 2 (LOXL2) is a copper and lysine tyrosyl-quinone (LTQ)-dependent amine oxidase belonging to the lysyl oxidase (LOX) family, the canonical function of which is to catalyze the crosslinking of elastin and collagen in the extracellular matrix (ECM). Many studies have revealed that the aberrant expression of LOXL2 in multiple cancers is associated with epithelial-mesenchymal transition (EMT), metastasis, poor prognosis, chemoradiotherapy resistance, and tumor progression. LOXL2 is regulated in many ways, such as transcriptional regulation, alternative splicing, microRNA regulation, posttranslational modification, and cleavage. Beyond affecting the extracellular environment, various intracellular roles, such as oxidation and deacetylation activities in the nucleus, have been reported for LOXL2. Additionally, LOXL2 contributes to tumor cell invasion by promoting cytoskeletal reorganization. Targeting LOXL2 has become a potential therapeutic strategy to combat many types of cancers. Here, we provide an overview of the regulation and downstream effectors of LOXL2 and discuss the intracellular role of LOXL2 in cancer.
赖氨酰氧化酶样蛋白 2(LOXL2)是一种铜和赖氨酸酪氨酸醌(LTQ)依赖性胺氧化酶,属于赖氨酰氧化酶(LOX)家族,其典型功能是催化细胞外基质(ECM)中弹性蛋白和胶原蛋白的交联。许多研究表明,LOXL2 在多种癌症中的异常表达与上皮-间充质转化(EMT)、转移、预后不良、化疗和放疗耐药以及肿瘤进展有关。LOXL2 的调控方式有很多,如转录调控、选择性剪接、microRNA 调控、翻译后修饰和切割。除了影响细胞外环境外,LOXL2 还具有多种细胞内作用,如在核内的氧化和去乙酰化活性。此外,LOXL2 通过促进细胞骨架重组促进肿瘤细胞侵袭。靶向 LOXL2 已成为对抗多种类型癌症的潜在治疗策略。在这里,我们概述了 LOXL2 的调控和下游效应子,并讨论了 LOXL2 在癌症中的细胞内作用。