Regulation of tumor cell – Microenvironment interaction by the autotaxin-lysophosphatidic acid receptor axis

Publication date: Available online 16 September 2018Source: Advances in Biological RegulationAuthor(s): Gabor J. Tigyi, Junming Yue, Derek D. Norman, Erzsebet Szabo, Andrea Balogh, Louisa Balazs, Guannan Zhao, Sue Chin LeeAbstractThe lipid mediator lysophosphatidic acid (LPA) in biological fluids is primarily produced by cleavage of lysophospholipids by the lysophospholipase D enzyme Autotaxin (ATX). LPA has been identified and abundantly detected in the culture medium of various cancer cell types, tumor effusates, and ascites fluid of cancer patients. Our current understanding of the physiological role of LPA established its role in fundamental biological responses that include cell proliferation, metabolism, neuronal differentiation, angiogenesis, cell migration, hematopoiesis, inflammation, immunity, wound healing, regulation of cell excitability, and the promotion of cell survival by protecting against apoptotic death. These essential biological responses elicited by LPA are seemingly hijacked by cancer cells in many ways; transcriptional upregulation of ATX leading to increased LPA levels, enhanced expression of multiple LPA GPCR subtypes, and the downregulation of its metabolic breakdown. Recent studies have shown that overexpression of ATX and LPA GPCR can lead to malignant transformation, enhanced proliferation of cancer stem cells, increased invasion and metastasis, reprogramming of the tumor microenvironment and the metastatic niche, and development of resistance to...
Source: Advances in Biological Regulation - Category: Biology Source Type: research