Figure 1
Current understanding of breast cancer progression mediated by ATX–LPA signalling axis. Autotaxin and LPA1–3 receptors are expressed in mammary glands and can exert multiple effects under physiological conditions. Lysophosphatidic acid is produce from lysophosphatidylcholine (LPC) by ATX and acts on the EDG-family LPA receptors, LPA1, LPA2 and LPA3. As an important pathway promoting cell survival, the ATX–LPA signalling axis may initiate tumourigenesis in breast by allow cells to be susceptible to other genetic mutations, leading to accumulation of several aberrant signalling pathways. Indeed, each of these components of the ATX–LPA signalling axis sufficiently induces tumourigenesis through upregulation of many signalling pathways, including PI3K, MAPK, Wnt/β-catenin and ER. In addition, marked increase in the production of several cytokines by LPA further advance the disease progression by local inflammation and angiogenesis. The effects of LPA on cytokine production and blood vessel formation may contribute to the metastasis of breast tumours to other tissues such as bone.
