Role of autotaxin in cancer stem cells

Abstract

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.

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Fig. 1
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Abbreviations

ATX:

Autotaxin

CSCs:

Cancer stem cells

LPA:

Lysophosphatidic acid

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Acknowledgments

This work was supported by the MRC program (NRF-2015R1A5A2009656 to J.K.), the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2018R1C1B6001290 to D.L.; NRF-2016R1D1A1B03935769 to D.S.), the National Cancer Institute of the USA (CA092160 to G.T.), and the Korea Health Technology R&D Project, Ministry of Health and Welfare (HI17C1635 to J.K.).

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Lee, D., Suh, D., Lee, S.C. et al. Role of autotaxin in cancer stem cells. Cancer Metastasis Rev 37, 509–518 (2018). https://doi.org/10.1007/s10555-018-9745-x

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Keywords

  • Lysophosphatidic acid
  • Lysophosphatidic acid receptor
  • Autotaxin
  • Cancer stem cells