Department of Medical Science, Pusan National University School of Medicine, Yangsan, 50612, South Korea.
Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Yangsan, 50612, South Korea.
Cancer Metastasis Rev. 2018 Sep;37(2-3):509-518. doi: 10.1007/s10555-018-9745-x.
Stem cells are a rare subpopulation defined by the potential to self-renew and differentiate into specific cell types. A population of stem-like cells has been reported to possess the ability of self-renewal, invasion, metastasis, and engraftment of distant tissues. This unique cell subpopulation has been designated as cancer stem cells (CSC). CSC were first identified in leukemia, and the contributions of CSC to cancer progression have been reported in many different types of cancers. The cancer stem cell hypothesis attempts to explain tumor cell heterogeneity based on the existence of stem cell-like cells within solid tumors. The elimination of CSC is challenging for most human cancer types due to their heightened genetic instability and increased drug resistance. To combat these inherent abilities of CSC, multi-pronged strategies aimed at multiple aspects of CSC biology are increasingly being recognized as essential for a cure. One of the most challenging aspects of cancer biology is overcoming the chemotherapeutic resistance in CSC. Here, we provide an overview of autotaxin (ATX), lysophosphatidic acid (LPA), and their signaling pathways in CSC. Increasing evidence supports the role of ATX and LPA in cancer progression, metastasis, and therapeutic resistance. Several studies have demonstrated the ATX-LPA axis signaling in different cancers. This lipid mediator regulatory system is a novel potential therapeutic target in CSC. In this review, we summarize the evidence linking ATX-LPA signaling to CSC and its impact on cancer progression and metastasis. We also provide evidence for the efficacy of cancer therapy involving the pharmacological inhibition of this signaling pathway.
干细胞是一种具有自我更新和分化为特定细胞类型潜能的稀有亚群。有报道称，存在一种具有自我更新、侵袭、转移和植入远处组织能力的干细胞样细胞群体。这种独特的细胞亚群被称为癌症干细胞（CSC）。CSC 最初在白血病中被鉴定出来，并且已经在许多不同类型的癌症中报道了 CSC 对癌症进展的贡献。癌症干细胞假说试图根据实体瘤中存在干细胞样细胞来解释肿瘤细胞异质性。由于大多数人类癌症类型的 CSC 具有较高的遗传不稳定性和增加的耐药性，因此消除 CSC 具有挑战性。为了对抗 CSC 的这些固有能力，针对 CSC 生物学多个方面的多管齐下的策略越来越被认为是治愈的关键。癌症生物学中最具挑战性的方面之一是克服 CSC 中的化疗耐药性。在这里，我们提供了一个概述，介绍了自分泌酶（ATX）、溶血磷脂酸（LPA）及其在 CSC 中的信号通路。越来越多的证据支持 ATX 和 LPA 在癌症进展、转移和治疗耐药性中的作用。几项研究已经证明了 ATX-LPA 轴信号在不同癌症中的作用。这个脂质介质调节系统是 CSC 中一个新的潜在治疗靶点。在这篇综述中，我们总结了将 ATX-LPA 信号与 CSC 联系起来的证据，以及它对癌症进展和转移的影响。我们还提供了涉及该信号通路药理学抑制的癌症治疗有效性的证据。
