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首页> 外文期刊>International Journal of Molecular Sciences >Beyond N-Cadherin, Relevance of Cadherins 5, 6 and 17 in Cancer Progression and Metastasis
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Beyond N-Cadherin, Relevance of Cadherins 5, 6 and 17 in Cancer Progression and Metastasis

机译：除了N-钙黏着蛋白外，钙黏着蛋白5、6和17在癌症进展和转移中的相关性

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Cell-cell adhesion molecules (cadherins) and cell-extracellular matrix adhesion proteins (integrins) play a critical role in the regulation of cancer invasion and metastasis. Although significant progress has been made in the characterization of multiple members of the cadherin superfamily, most of the published work continues to focus in the switch E-/N-cadherin and its role in the epithelial–mesenchymal transition. Here, we will discuss the structural and functional properties of a subset of cadherins (cadherin 17, cadherin 5 and cadherin 6) that have an RGD motif in the extracellular domains. This RGD motif is critical for the interaction with α2β1 integrin and posterior integrin pathway activation in cancer metastatic cells. However, other signaling pathways seem to be affected by RGD cadherin interactions, as will be discussed. The range of solid tumors with overexpression or “de novo” expression of one or more of these three cadherins is very wide (gastrointestinal, gynaecological and melanoma, among others), underscoring the relevance of these cadherins in cancer metastasis. Finally, we will discuss different evidences that support the therapeutic use of these cadherins by blocking their capacity to work as integrin ligands in order to develop new cures for metastatic patients.
机译：细胞-细胞粘附分子（钙黏着蛋白）和细胞-细胞外基质粘附蛋白（整合素）在调节癌症的侵袭和转移中起着至关重要的作用。尽管在钙粘着蛋白超家族的多个成员的鉴定方面已取得了重大进展，但大多数已发表的工作仍集中在E- / N-钙粘着蛋白开关及其在上皮-间充质转化中的作用。在这里，我们将讨论在细胞外域具有RGD图案的钙粘蛋白子集（钙粘蛋白17，钙粘蛋白5和钙粘蛋白6）的结构和功能特性。该RGD基序对于在癌症转移细胞中与α2β1整合素相互作用和后整合素途径激活至关重要。然而，正如将要讨论的那样，其他信号传导途径似乎也受到RGD钙粘蛋白相互作用的影响。具有这三种钙黏着蛋白中的一种或多种的过表达或“从头”表达的实体瘤的范围非常广泛（胃肠道，妇科和黑色素瘤等），强调了这些钙黏着蛋白与癌症转移的相关性。最后，我们将讨论通过阻断钙粘蛋白作为整联蛋白配体起作用的能力来支持这些钙粘蛋白的治疗用途的不同证据，以便为转移性患者开发新的治疗方法。

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