文章：

CD44：致癌细胞能从一个丰富表达的分子中获益吗？

CD44: can a cancer-initiating cell profit from an abundantly expressed molecule?

原文发布日期：2011-03-10

DOI: 10.1038/nrc3023

类型: Review Article

开放获取: 否

要点：

1. CD44, the major hyaluronan (HA) receptor, makes abundant use of alternative splicing and can be located in glycolipid-enriched microdomains (GEMs). The extracellular and the cytoplasmic domains can associate with a large array of molecules.
2. Cancer-initiating cells (CICs; also known as cancer stem cells) constitute a minor population of cells within a tumour, but are frequently essential for tumour maintenance and progression. CICs can be enriched by so-called CIC markers, the most common of which is CD44.
3. CD44 can contribute to the activation of stem cell regulatory genes and can be a target of these genes, but there is, at present, no compelling evidence that CD44 has a central role in self-renewal and maintenance of pluripotency.
4. CD44 binding to HA has an important role in haematopoietic stem cells (HSCs) and leukaemia-initiating cells (LICs) and probably CIC homing and adhesion. HA binding-induced changes in CD44 membrane localization and conformation trigger the association and activation of multiple signal transduction molecules and of proteases, which supports migration.
5. CD44 accounts for the homing and settling of adult stem cells (ASCs), as well as metastasizing tumour cells and CICs in the niche, is actively involved in niche assembly through its effect on HA secretion and degradation, mainly owing to its activity as a catcher of chemokines, growth factors and matrix-degrading enzymes.
6. The HA–CD44 and HA–CD44v interactions have a central role in receptor tyrosine kinase (RTK)-induced activation of anti-apoptotic pathways and actively promote tumour cell and possibly CIC survival through their associations with multidrug resistance genes. Importantly, activation of signalling pathways initiated by the tumour matrix could be inhibited by HA degradation, by competition with small HA fragments, by CD44 blockade or by CD44 knockdown, whereas a blockade of an individual RTK did not recapitulate all of the effects observed on inhibition of CD44–HA binding.

要点翻译：

1. CD44作为主要的透明质酸（HA）受体，广泛利用选择性剪接机制，并可定位于糖脂富集微区（GEMs）。其胞外结构域和胞质结构域能与多种分子结合。
2. 肿瘤起始细胞（CICs，亦称肿瘤干细胞）在肿瘤中仅占少数群体，但对肿瘤维持和进展往往至关重要。通过所谓的CIC标志物可富集这类细胞，其中最常见的标志物是CD44。
3. CD44既能促进干细胞调控基因的激活，也可作为这些基因的靶标，但目前尚无确凿证据表明CD44在自我更新和多能性维持中起核心作用。
4. CD44与HA的结合在造血干细胞（HSCs）、白血病起始细胞（LICs）以及可能的CIC归巢与黏附过程中发挥重要作用。HA结合诱导的CD44膜定位与构象变化，可触发多种信号转导分子和蛋白酶的聚集与激活，从而促进细胞迁移。
5. CD44不仅负责成体干细胞（ASCs）、转移性肿瘤细胞及CICs在微环境中的归巢与定植，还通过调控HA分泌与降解（主要凭借其捕获趋化因子、生长因子和基质降解酶的能力）积极参与微环境组装。
6. HA-CD44和HA-CD44v相互作用在受体酪氨酸激酶（RTK）诱导的抗凋亡通路激活中具有核心地位，并通过与多药耐药基因的关联主动促进肿瘤细胞及潜在CICs的存活。重要的是，肿瘤基质引发的信号通路激活可通过以下方式抑制：HA降解、小分子HA片段竞争性结合、CD44阻断或CD44基因敲低，而单一RTK的阻断并不能复现抑制CD44-HA结合所观察到的全部效应。

英文摘要：

Can an abundantly expressed molecule be a reliable marker for the cancer-initiating cells (CICs; also known as cancer stem cells), which constitute the minority of cells within the mass of a tumour? CD44 has been implicated as a CIC marker in several malignancies of haematopoietic and epithelial origin. Is this a fortuitous coincidence owing to the widespread expression of the molecule or is CD44 expression advantageous as it fulfils some of the special properties that are displayed by CICs, such as self-renewal, niche preparation, epithelial–mesenchymal transition and resistance to apoptosis?

摘要翻译： 

一个大量表达的分子能否成为肿瘤起始细胞（CICs，又称癌症干细胞）的可靠标志物？这些细胞在肿瘤整体中仅占少数。CD44已被证实是造血系统和上皮来源多种恶性肿瘤的CIC标志物。这究竟是源于该分子广泛表达的偶然巧合，还是CD44表达本身具有优势，因其恰好满足了CICs表现出的某些特殊属性——如自我更新、微环境构建、上皮-间质转化以及抗凋亡能力？

原文链接：

CD44: can a cancer-initiating cell profit from an abundantly expressed molecule?