文章：

肿瘤中钙粘蛋白和 Ig-CAMs的细胞粘附和信号传导

Cell adhesion and signalling by cadherins and Ig-CAMs in cancer

原文发布日期：2004-02-01

DOI: 10.1038/nrc1276

类型: Review Article

开放获取: 否

要点：

1. Cell-adhesion molecules of the cadherin and immunoglobulin-like cell-adhesion molecule (Ig-CAM) superfamilies not only exert their functions by mediating cell–cell and cell–matrix adhesion, but also by directly eliciting signals that are involved in tissue morphogenesis and tumour progression.
2. In addition, signalling molecules are also able to modulate the adhesion status of the cell by acting on cell-adhesion molecules themselves, or on other components of signalling complexes.
3. The function of epithelial (E)-cadherin is altered in most epithelial tumours during the progression to tumour malignancy. E-cadherin function can be disrupted by various genetic and epigenetic mechanisms, including modulation by signalling molecules.
4. Loss of E-cadherin function elicits active signals that support tumour-cell migration, invasion and metastatic dissemination.
5. In several cancer types, loss of E-cadherin function is accompanied by the gain of expression of mesenchymal cadherins, for example, neuronal (N)-cadherin and cadherin-11, in a process that is known as the cadherin switch.
6. N-cadherin interacts with members of the fibroblast growth factor receptor (FGFR) family, thereby inducing pro-migratory and invasive signalling cascades.
7. Neural CAM (NCAM) also associates with FGFRs. Loss of NCAM function during tumour progression affects cell–matrix adhesion through the loss of FGFR-induced, integrin-mediated cell–matrix adhesion.
8. Several other members of the cadherin and Ig-CAM families interact with signalling molecules, thereby modulating physiological and pathological processes.

要点翻译：

1. 钙粘蛋白和免疫球蛋白样细胞粘附分子（Ig-CAM）超家族的细胞粘附分子不仅通过介导细胞-细胞和细胞-基质粘附发挥作用，还能通过直接引发参与组织形态发生和肿瘤进展的信号传导来实现功能。
2. 此外，信号分子也能够通过作用于细胞粘附分子本身或信号复合物的其他组分来调节细胞的粘附状态。
3. 在上皮性肿瘤向恶性肿瘤进展的过程中，大多数上皮性肿瘤中的上皮钙粘蛋白（E-cadherin）功能会发生改变。E-钙粘蛋白功能可通过多种遗传和表观遗传机制被破坏，包括信号分子的调控。
4. E-钙粘蛋白功能的丧失会引发支持肿瘤细胞迁移、侵袭和转移扩散的活性信号。
5. 在几种癌症类型中，E-钙粘蛋白功能的丧失伴随着间质钙粘蛋白（例如神经钙粘蛋白（N-cadherin）和钙粘蛋白-11）表达的获得，这一过程被称为钙粘蛋白转换。
6. N-钙粘蛋白与成纤维细胞生长因子受体（FGFR）家族成员相互作用，从而诱导促迁移和侵袭的信号级联反应。
7. 神经细胞粘附分子（NCAM）也与FGFRs相关。肿瘤进展过程中NCAM功能的丧失通过失去FGFR诱导的、整合素介导的细胞-基质粘附来影响细胞-基质粘附。
8. 钙粘蛋白和Ig-CAM家族的其他几个成员与信号分子相互作用，从而调节生理和病理过程。

英文摘要：

In addition to their adhesive functions, cell-adhesion molecules modulate signal-transduction pathways by interacting with molecules such as receptor tyrosine kinases, components of the WNT signalling pathway and RHO-family GTPases. So, changes in the expression of cell-adhesion molecules affect not only the adhesive repertoire of a cell, but also its signal-transduction status. Conversely, signalling pathways can modulate the function of cell-adhesion molecules, altering the interactions between cells and their environment. Recent experimental evidence indicates that such processes have a crucial role in tumour progression, in particular during invasion and metastasis.

摘要翻译： 

除了黏附功能外，细胞黏附分子还能通过与受体酪氨酸激酶、WNT信号通路组分及RHO家族GTP酶等分子相互作用，调控信号转导通路。因此，细胞黏附分子表达的改变不仅影响细胞的黏附谱，也改变其信号转导状态。反之，信号通路也能调节细胞黏附分子的功能，改变细胞与其环境的相互作用。最新实验证据表明，这些过程在肿瘤进展，特别是侵袭和转移中具有关键作用。

原文链接：

Cell adhesion and signalling by cadherins and Ig-CAMs in cancer