Biology and function of the autotaxin/lysophosphatidic acid axis in cancer (Review)

Autotaxin (ATX) lysophospholipase D has been identified as an 'autocrine motility factor' for tumour cells. The tumour microenvironment (TME) serves a critical role in cancer development, with ATX, as a component of the ATX/lysophosphatidic acid (LPA) axis, integrated into a complex network of molecular signalling. This axis is particularly significant because it activates multiple overlapping signal transduction pathways, thereby mediating pleiotropic effects across nearly all cell types within the TME. The ATX/LPA pathway has multiple molecular and cellular drivers, making the signalling mechanisms activated by ATX/LPA an interesting subject for evaluation in cancer development. The present review discusses the multiple effects of ATX/LPA on three macroevents involving several TME components: i) Inflammation and immunity; ii) cellular proliferation and metabolism; and iii) invasion and metastasis. The aim of the present review was to highlight the clinical impact of the ATX/LPA pathways in the pathogenesis of cancer. Clarifying the role of ATX and blocking this pathway in the inflammatory cycle may open novel therapeutic avenues to improve cancer treatment. Although several reviews have addressed the ATX/LPA axis in cancer, most have focused primarily on its roles in tumour growth, migration and metastasis. By contrast, the present review provides an updated, integrative perspective that emphasizes recent advances (2020-2025) regarding the role of the ATX/LPA axis in shaping the immunometabolic landscape of the TME, with particular attention to inflammation-driven immune regulation.