Mediators of Inflammation / 2017 / Article / Fig 3

Review Article

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 Gαq/11, Gαi/0, and Gα12/13. Gαq/11 induces NFκB activation through PKCδ promoting TNF-α, IL-8, and IL-6 production. Gαi/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. Gαi/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, Gα12/13/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).

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