Abstract
Lysophosphatidic acid (LPA) is a potent lipid mediator that acts on a series of specific G protein-coupled receptors, leading to diverse biological actions. Lysophosphatidic acid induces cell proliferation, survival and migration, which are critically required for tumour formation and metastasis. This bioactive lipid is produced by the ectoenzyme lysophospholipase D or autotaxin (ATX), earlier known as an autocrine motility factor. The ATX-LPA signalling axis has emerged as an important player in many types of cancer. Indeed, aberrant expression of ATX and LPA receptors occurs during the development and progression of breast cancer. Importantly, expression of either ATX or LPA receptors in the mammary gland of transgenic mice is sufficient to induce the development of a high frequency of invasive and metastatic mammary cancers. The focus of research now turns to understanding the mechanisms by which ATX and LPA promote mammary tumourigenesis and metastasis. Targeting the ATX-LPA signalling axis for drug development may further improve outcomes in patients with breast cancer.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Breast Neoplasms / etiology*
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Cell Transformation, Neoplastic* / drug effects
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Cell Transformation, Neoplastic* / genetics
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Disease Progression
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Female
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Humans
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Lysophospholipids / metabolism*
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Lysophospholipids / pharmacology
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Lysophospholipids / physiology*
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Mice
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Models, Biological
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Multienzyme Complexes / genetics
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Multienzyme Complexes / physiology
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Phosphodiesterase I / genetics
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Phosphodiesterase I / physiology
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Phosphoric Diester Hydrolases
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Pyrophosphatases / genetics
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Pyrophosphatases / physiology
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Receptors, Lysophosphatidic Acid / genetics
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Receptors, Lysophosphatidic Acid / metabolism
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Receptors, Lysophosphatidic Acid / physiology
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Signal Transduction / drug effects
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Signal Transduction / genetics
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Signal Transduction / physiology
Substances
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Lysophospholipids
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Multienzyme Complexes
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Receptors, Lysophosphatidic Acid
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Phosphoric Diester Hydrolases
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Phosphodiesterase I
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alkylglycerophosphoethanolamine phosphodiesterase
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Pyrophosphatases
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lysophosphatidic acid