The role of type II transmembrane serine protease-mediated signaling in cancer.
The role of type II transmembrane serine protease-mediated signaling in cancer.
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DOI：
10.1111/febs.13971
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发表时间：
2017-05
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影响因子：
--
通讯作者：
List K
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作者：
Tanabe LM;List K
细胞周蛋白酶长期以来一直与癌症发生有关。以前的研究集中在这些蛋白质上，主要是作为细胞外基质（ECM）蛋白降解酶，使癌细胞能够突破基底膜并侵入周围组织。然而，最近，细胞表面蛋白酶，包括丝氨酸蛋白酶，作为特定靶点的蛋白水解修饰剂的观点发生了转变，所述靶点包括生长因子和蛋白酶激活的受体，其对于致癌信号传导途径的激活至关重要。在目前鉴定的176种人丝氨酸蛋白酶中，17种的子集被称为II型跨膜丝氨酸蛋白酶（TTSP），许多已被证明与癌症进展相关，因为它们在世纪之交首次被鉴定为一个家族。为此，TTSP的表达改变似乎是几种肿瘤类型的标志。然而，底物和潜在的信号通路仍不清楚。这些蛋白质定位于细胞表面使它们处于介导细胞与其周围环境之间的信号转导的独特位置。许多TTSP已经被证明在出生后发育，组织稳态和肿瘤进展等过程中发挥关键作用，这些过程具有重叠的分子机制。在这篇综述中，我们总结了目前的知识TTSP家族在促癌信号转导中的作用。II型跨膜丝氨酸蛋白酶（TTSP）的表达改变是几种类型肿瘤的特征。TTSP是靶点如生长因子和蛋白酶激活受体的蛋白水解修饰剂，其对于致癌信号通路的激活至关重要。定位于细胞表面，TTSPS介导细胞与其周围环境之间的信号转导。许多研究表明，TTSP代表了癌症治疗干预的一种有前途的选择。
Pericellular proteases have long been implicated in carcinogenesis. Previous research focused on these proteins, primarily as extracellular matrix (ECM) protein degrading enzymes which allowed cancer cells to breach the basement membrane and invade surrounding tissue. However, recently, there has been a shift in the view of cell surface proteases, including serine proteases, as proteolytic modifiers of particular targets, including growth factors and protease-activated receptors, which are critical for the activation of oncogenic signaling pathways. Of the 176 human serine proteases currently identified, a subset of 17 known as type II transmembrane serine proteases (TTSPs), many have been shown to be relevant to cancer progression, since they were first identified as a family around the turn of the century. To this end, altered expression of TTSPs appeared as a trademark of several tumor types. However, the substrates and underlying signaling pathways remained unclear. Localization of these proteins to the cell surface places them in the unique position to mediate signal transduction between the cell and its surrounding environment. Many of the TTSPs have already been shown to play key roles in processes such as postnatal development, tissue homeostasis, and tumor progression, which share overlapping molecular mechanisms. In this review, we summarize the current knowledge regarding the role of the TTSP family in pro-oncogenic signaling. Altered expression of type II transmembrane serine proteases (TTSP) is a feature of several types of tumors. TTSPs are proteolytic modifiers of targets such as growth factors and protease-activated receptors, which are critical for the activation of oncogenic signaling pathways. Localized to the cell surface, TTSPS mediate signal transduction between the cell and its surrounding environment. Numerous studies suggest that TTSPs represent a promising option for therapeutic intervention of cancer.