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Special Issue "Lysophosphatidic Acid Signaling in Health and Disease"

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Guest Editor

Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Interests: mitochondria; premature aging; DNA-PKcs; MOMP; lysophosphatidic acid; DNA repair

Prof. Dr. Hsinyu Lee

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Guest Editor

Department of Life Science, National Taiwan University, Taipei 10617, Taiwan
Interests: cancer biology; angiogenesis; lysophosphatidic acid; lysophosphatidic acid receptors; aryl hydrocarbon receptor; cell aging; bioengineering
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Dear Colleagues,

Lysophosphatidic acid (LPA) is a small phospholipid acting as an extracellular lipid-controlling hormone. LPA mediates cellular apoptosis, invasion, and migration by activating its six G protein-coupled receptors (LPARs). LPA and LPARs mediate a broad range of biological effects in many tissue types. An abnormal level of LPA or LPARs has been shown to impair development and individual healthiness. For instance, LPA and LPARs have diverse effects on the development of the nervous system and cardiovascular system. In addition, LPA signaling has been suggested to be a potent signaling pathway with wide-ranging effects on the aging process. Besides, high levels of LPA are found in the tumor microenvironment. LPA has been suggested as an essential factor for the survival and growth of cancer cells. However, the roles of LPA in antitumor therapy remain vastly unexplored. Taken together, this Special Issue aims to update the current understandings about the roles of LPA and LPARs in human health and diseases.

Dr. Wei-Min Chen
Prof. Dr. Hsinyu Lee
Guest Editors

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Open AccessArticle

Lysophosphatidic Acid Receptor Signaling in the Human Breast Cancer Tumor Microenvironment Elicits Receptor-Dependent Effects on Tumor Progression

Matthew G. K. Benesch

and

Int. J. Mol. Sci. 2023, 24(12), 9812; https://doi.org/10.3390/ijms24129812 - 06 Jun 2023

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Abstract

Lysophosphatidic acid receptors (LPARs) are six G-protein-coupled receptors that mediate LPA signaling to promote tumorigenesis and therapy resistance in many cancer subtypes, including breast cancer. Individual-receptor-targeted monotherapies are under investigation, but receptor agonism or antagonism effects within the tumor microenvironment following treatment are minimally understood. In this study, we used three large, independent breast cancer patient cohorts (TCGA, METABRIC, and GSE96058) and single-cell RNA-sequencing data to show that increased tumor LPAR1, LPAR4, and LPAR6 expression correlated with a less aggressive phenotype, while high LPAR2 expression was particularly associated with increased tumor grade and mutational burden and decreased survival. Through gene set enrichment analysis, it was determined that cell cycling pathways were enriched in tumors with low LPAR1, LPAR4, and LPAR6 expression and high LPAR2 expression. LPAR levels were lower in tumors over normal breast tissue for LPAR1, LPAR3, LPAR4, and LPAR6, while the opposite was observed for LPAR2 and LPAR5. LPAR1 and LPAR4 were highest in cancer-associated fibroblasts, while LPAR6 was highest in endothelial cells, and LPAR2 was highest in cancer epithelial cells. Tumors high in LPAR5 and LPAR6 had the highest cytolytic activity scores, indicating decreased immune system evasion. Overall, our findings suggest that potential compensatory signaling via competing receptors must be considered in LPAR inhibitor therapy. Full article

(This article belongs to the Special Issue Lysophosphatidic Acid Signaling in Health and Disease)

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Entering, Linked with the Sphinx: Lysophosphatidic Acids Everywhere, All at Once, in the Oral System and Cancer

D. Roselyn Cerutis

Michael D. Weston

and

Takanari Miyamoto

Int. J. Mol. Sci. 2023, 24(12), 10278; https://doi.org/10.3390/ijms241210278 - 17 Jun 2023

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Abstract

Oral health is crucial to overall health, and periodontal disease (PDD) is a chronic inflammatory disease. Over the past decade, PDD has been recognized as a significant contributor to systemic inflammation. Here, we relate our seminal work defining the role of lysophosphatidic acid (LPA) and its receptors (LPARs) in the oral system with findings and parallels relevant to cancer. We discuss the largely unexplored fine-tuning potential of LPA species for biological control of complex immune responses and suggest approaches for the areas where we believe more research should be undertaken to advance our understanding of signaling at the level of the cellular microenvironment in biological processes where LPA is a key player so we can better treat diseases such as PDD, cancer, and emerging diseases. Full article

(This article belongs to the Special Issue Lysophosphatidic Acid Signaling in Health and Disease)

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