CD44 is a transmembrane glycoprotein expressed in several healthy and tumor tissues. Modifications in its structure contribute differently to the activity of this molecule. One modification that has provoked interest is the consecutive cleavage of the CD44 extracellular ectodomain by enzymes that belong mainly to the family of metalloproteases. This process releases biologically active substrates, via alternative splice forms of CD44, that generate CD44v3 or v6 isoforms which participate in the transcriptional regulation of genes and proteins associated to signaling pathways involved in the development of cancer. These include the protooncogene tyrosine-protein kinase Src (c-Src)/signal transducer and activator of transcription 3 (STAT3), the epithelial growth factor receptor, the estrogen receptor, Wnt/βcatenin, or Hippo signaling pathways all of which are associated to cell proliferation, differentiation, or cancer progression. Whereas CD44 still remains as a very useful prognostic cell marker in different pathologies, the main topic is that the generation of CD44 intracellular fragments assists the regulation of transcriptional proteins involved in the cell cycle, cell metabolism, and most importantly, the regulation of some stem cell-associated markers.

中文翻译：

---

CD44的蛋白水解过程及其在癌症中的意义

CD44是在几种健康和肿瘤组织中表达的跨膜糖蛋白。其结构的修饰对该分子活性的贡献不同。引起人们兴趣的一种修饰是主要属于金属蛋白酶家族的酶对CD44细胞外结构域的连续切割。此过程通过CD44的可变剪接形式释放生物活性底物，该底物产生CD44v3或v6同工型，这些同工型参与与癌症发展相关的信号通路相关的基因和蛋白质的转录调控。这些包括原癌基因酪氨酸蛋白激酶Src（c-Src）/信号转导子和转录激活子3（STAT3），上皮生长因子受体，雌激素受体Wnt / β连环蛋白或Hippo信号通路均与细胞增殖，分化或癌症进展相关。尽管CD44在各种病理学中仍然是非常有用的预后细胞标志物，但主要主题是CD44细胞内片段的产生有助于调节参与细胞周期，细胞代谢以及最重要的是调节某些干细胞的转录蛋白。细胞相关标记。