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.
