Cancer and Metastasis Reviews

, Volume 37, Issue 2–3, pp 509–518 | Cite as

Role of autotaxin in cancer stem cells

  • Dongjun Lee
  • Dong-Soo Suh
  • Sue Chin Lee
  • Gabor J. Tigyi
  • Jae Ho KimEmail author


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.


Lysophosphatidic acid Lysophosphatidic acid receptor Autotaxin Cancer stem cells 





Cancer stem cells


Lysophosphatidic acid



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.).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Dongjun Lee
    • 1
  • Dong-Soo Suh
    • 2
  • Sue Chin Lee
    • 3
  • Gabor J. Tigyi
    • 3
  • Jae Ho Kim
    • 4
    Email author
  1. 1.Department of Medical SciencePusan National University School of MedicineYangsanSouth Korea
  2. 2.Department of Obstetrics and GynecologyPusan National University School of MedicineYangsanSouth Korea
  3. 3.Department of PhysiologyUniversity of Tennessee Health Science CenterMemphisUSA
  4. 4.Department of PhysiologyPusan National University School of MedicineYangsanRepublic of Korea

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