细胞从其微环境接收到的大量信号的接收和整合决定了细胞的命运。CD44作为透明质酸和许多其他细胞外基质成分的受体，以及生长因子和细胞因子的辅因子，因此，CD44是一个信号平台，它将细胞微环境信号与生长因子和细胞因子信号整合在一起，并将信号传导到膜相关的细胞骨架蛋白或细胞核，以调节与细胞-基质粘附相关的多种基因表达水平，细胞迁移，扩散,分化,和生存。越来越多的证据表明CD44，尤其是CD44v亚型，是癌症干细胞（CSC）标记和调节CSC特性的关键参与者，包括自我更新,肿瘤起始，转移,和化学放射抗性。此外，有充分的证据表明CD44，特别是CD44v亚型，是各种类型肿瘤的有价值的预后标志物。因此,靶向CD44的疗法可能会破坏CSC群体，这对治愈危及生命的癌症大有希望。然而,在确定如何最好地使用CD44作为生物标志物和治疗靶点方面,仍存在许多挑战.在这里，我们总结了CD44/CD44v在癌症干性调节中的关键作用以及CD44/CD44v作为癌症生物标志物和治疗靶标的研究现状。我们还讨论了可能导致CD44/CD44v在临床应用中的最佳使用的当前挑战和未来方向。
结论：越来越多的证据表明，癌症干细胞（CSCs）是癌症侵袭性的主要原因，耐药性,和肿瘤复发。CD44，尤其是CD44v亚型，已被鉴定为用于分离和富集不同类型癌症中的CSC的CSC表面标志物。综述了CD44/CD44v在肿瘤干性调控中的重要作用以及CD44/CD44v作为肿瘤生物标志物和治疗靶点的研究现状。还讨论了可能导致CD44/CD44v在临床应用中的最佳使用的当前挑战和未来方向。
The reception and integration of the plethora of signals a cell receives from its microenvironment determines the cell\'s fate. CD44 functions as a receptor for hyaluronan and many other extracellular matrix components, as well as a cofactor for growth factors and cytokines, and thus, CD44 is a signaling platform that integrates cellular microenvironmental cues with growth factor and cytokine signals and transduces signals to membrane-associated cytoskeletal proteins or to the nucleus to regulate a variety of gene expression levels related to cell-matrix adhesion, cell migration, proliferation, differentiation, and survival. Accumulating evidence indicates that CD44, especially CD44v isoforms, are cancer stem cell (CSC) markers and critical players in regulating the properties of CSCs, including self-renewal, tumor initiation, metastasis, and chemoradioresistance. Furthermore, there is ample evidence that CD44, especially CD44v isoforms, are valuable prognostic markers in various types of tumors. Therefore, therapies that target CD44 may destroy the CSC population, and this holds great promise for the cure of life-threatening cancers. However, many challenges remain to determining how best to use CD44 as a biomarker and therapeutic target. Here we summarize the current findings concerning the critical role of CD44/CD44v in the regulation of cancer stemness and the research status of CD44/CD44v as biomarkers and therapeutic targets in cancer. We also discuss the current challenges and future directions that may lead to the best use of CD44/CD44v for clinical applications.
CONCLUSIONS: Mounting evidence indicates that cancer stem cells (CSCs) are mainly responsible for cancer aggressiveness, drug resistance, and tumor relapse. CD44, especially CD44v isoforms, have been identified as CSC surface markers for isolating and enriching CSCs in different types of cancers. The current findings concerning the critical role of CD44/CD44v in regulation of cancer stemness and the research status of CD44/CD44v as biomarkers and therapeutic targets in cancer are summarized. The current challenges and future directions that may lead to best use of CD44/CD44v for clinical applications are also discussed.
PDF(Sci-hub)