Autotaxin-Lysophosphatidic Acid: From Inflammation to Cancer Development

Figure 3

ATX-LPA axis promotes cancer-related inflammation. In CRI, LPA acts on its receptors via Gα_q/11, Gα_i/0, and Gα_12/13. Gα_q/11 induces NFκB activation through PKCδ promoting TNF-α, IL-8, and IL-6 production. Gα_i/0 induces the PI3K/AKT/mTOR pathway culminating in NFκB and HIF-1α translocation to the nucleus. HIF-1α induces the transcription of TERT enabling replicative immortality. Gα_i/0 can also transactivate Src kinase and crosstalk with EGFR, to induce extracellular matrix degrading proteins, and STAT-3 signaling pathway to further induce cytokine production. PI3K signaling promotes ROS production and activation of AKT, ERK1/2, and NFκB. On the other hand, Gα_12/13/RhoA/ROCK signaling causes activation of transcription factor ATF2 to induce further proinflammatory mediator production. Finally, cytokine production, particularly IL-6, can interact with their IL receptors and promote STAT5 and STAT3 activation. In all, these pathways maintain a proinflammatory environment that leads to malignant transformation. Dashed lines denote that other proteins participate in the pathways and were omitted to summarize information. This figure is reproduced from Liu et al. [124] (under the Creative Commons Attribution License/public domain).