Sortilin is a key component of exos

Sortilin is a key component of exosome biogenesis

Unprecedented reports have found that sortilin expres-sion level is associated to different types of cancer.24-26

Some of these studies have implicated that sortilin could play a role in the tumorigenesis process.24,26 Our team
has been interested in these links between sortilin and cancer and at the same time the cross-talk between the epidermal growth factor receptor (EGFR) and tyrosine kinase receptor (Trk) signaling pathways.13 We have dis-covered that sortilin can form a novel complex with TrkB and EGFR found in exosomes that are released from lung cancer cells conveying a microenvironmental control upon endothelial cells.39 In this study, we exam-ined closely the secretion mechanism utilized for the extracellular domain of sortilin from human lung cancer cells (A549) and the effect on the microenvironment. We show for the first time that sortilin uses a ‘canonical pathway’ and can be found in exosomes. We demon-strate that sortilin is a key component of exosomes medi-ating communication between A549 and endothelial cells (Figure 2). Sortilin is already known to play a prime function in cancer cells; however we have reported herein that it plays a new role in both the assembly of a tyrosine kinase complex and its exosome release. This novel complex called ‘TES’ complex expressed by exo-somes results in the linkage of two tyrosine kinase recep-tors, TrkB and EGFR with sortilin. We demonstrate in this study that the TES complex coveys a control on the microenvironment i.e. endothelial cells and initiates the activation of angiogenesis via exosome transfer. There-fore, our data suggested that sortilin and its partners have a paracrine through exosome transfer and control of the microenvironment. This novel complex contain-ing sortilin could play the role as a molecular switch in cancer progression by promoting angiogenesis.

結果 (中文) 1:

Sortilin 是一个关键组成部分的外切体生源前所未有的报告发现，sortilin 表达 sion 水平是关联到不同类型的 cancer.24-26一些这些研究有牵连，sortilin 可以在发挥作用肿瘤 process.24,26 我们的团队has been interested in these links between sortilin and cancer and at the same time the cross-talk between the epidermal growth factor receptor (EGFR) and tyrosine kinase receptor (Trk) signaling pathways.13 We have dis-covered that sortilin can form a novel complex with TrkB and EGFR found in exosomes that are released from lung cancer cells conveying a microenvironmental control upon endothelial cells.39 In this study, we exam-ined closely the secretion mechanism utilized for the extracellular domain of sortilin from human lung cancer cells (A549) and the effect on the microenvironment. We show for the first time that sortilin uses a ‘canonical pathway’ and can be found in exosomes. We demon-strate that sortilin is a key component of exosomes medi-ating communication between A549 and endothelial cells (Figure 2). Sortilin is already known to play a prime function in cancer cells; however we have reported herein that it plays a new role in both the assembly of a tyrosine kinase complex and its exosome release. This novel complex called ‘TES’ complex expressed by exo-somes results in the linkage of two tyrosine kinase recep-tors, TrkB and EGFR with sortilin. We demonstrate in this study that the TES complex coveys a control on the microenvironment i.e. endothelial cells and initiates the activation of angiogenesis via exosome transfer. There-fore, our data suggested that sortilin and its partners have a paracrine through exosome transfer and control of the microenvironment. This novel complex contain-ing sortilin could play the role as a molecular switch in cancer progression by promoting angiogenesis.

結果 (中文) 3:

细胞凋亡是exosome生物合成的关键部件
前所未有的报告发现，sortilin的表达水平是不同类型的cancer.24-26相关
有些研究表明sortilin可能在肿瘤发生发展过程中起着重要的作用。其我们的团队
同时具有表皮生长因子受体之间的串扰是sortilin和癌症之间的这些联系感兴趣（EGFR）和酪氨酸激酶受体（TRK）信号pathways.13我们已经发现了，可以与TrkB和EGFR sortilin发现exosomes是从肺癌细胞对内皮cells.39输送微环境控制在这发布的研究形成一个新的复杂的检验，我们密切用于从人肺癌细胞sortilin胞外结构域的分泌机制（A549）和微环境的影响。我们第一次显示，sortilin使用规范途径，可以发现在其。我们表明，细胞凋亡是一个关键组成部分的外来中介沟通A549细胞和内皮细胞（图2）。细胞凋亡是已知在癌细胞起主要作用；但是我们有报告，在装配一个酪氨酸激酶复合物及其胞外体释放扮演新的角色。这部小说被称为“测试”的复杂复杂出一些结果在两个酪氨酸激酶受体TrkB表达的联动，表皮生长因子受体与sortilin。我们证明在这项研究中，测试复杂的人群对微血管内皮细胞，启动控制即通过外泌体转移血管生成激活。因此，我们的数据表明，sortilin及其合作伙伴通过外泌体转移和微环境控制有分泌。这种新的复杂的含有sortilin可以通过促进血管生成在肿瘤进展的分子开关的作用。