Article
Medicine, Research & Experimental
Jessica M. Konen, B. Leticia Rodriguez, Haoyi Wu, Jared J. Fradette, Laura Gibson, Lixia Diao, Jing Wang, Stephanie Schmidt, Ignacio I. Wistuba, Jianjun Zhang, Don L. Gibbons
Summary: Non-small cell lung cancers with KRAS and TP53 mutations show partial response to anti-PD-(L)1 treatment, but most patients do not experience durable clinical benefit. In this study, mouse lung cancer models with intrinsic resistance to anti-PD-1 were developed, and differential gene expression was analyzed to identify novel resistance mechanisms. It was found that the enzyme autotaxin (ATX) and the metabolite lysophosphatidic acid (LPA) were upregulated in resistant tumors and negatively correlated with CD8+ T cell infiltration. Inhibition of ATX or its downstream receptor LPAR5, in combination with anti-PD-1, effectively restored the anti-tumor immune response and controlled tumor growth. These findings suggest that the ATX/LPA axis is an immunosuppressive pathway that hampers the response to immune checkpoint blockade in lung cancer.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Multidisciplinary Sciences
Koji Murakami, Tsutomu Tamada, Daisuke Saigusa, Eisaku Miyauchi, Masayuki Nara, Masakazu Ichinose, Makoto Kurano, Yutaka Yatomi, Hisatoshi Sugiura
Summary: This study found that urine ATX levels may be a novel and useful indicator for assessing disease activity in sarcoidosis.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Elisa Matas-Rico, Elselien Frijlink, Irene van der Haar Avila, Apostolos Menegakis, Maaike van Zon, Andrew J. Morris, Jan Koster, Fernando Salgado-Polo, Sander de Kivit, Telma Lanc, Antonio Mazzocca, Zoe Johnson, John Haanen, Ton N. Schumacher, Anastassis Perrakis, Inge Verbrugge, Joost H. van den Berg, Jannie Borst, Wouter H. Moolenaar
Summary: The study reveals that ATX secreted by melanoma cells repels tumor-infiltrating lymphocytes and circulating CD8(+) T cells, acting as a chaperone for LPA. Mechanistically, T cell repulsion is mainly involved G alpha(12/13)-coupled LPAR6, suppressing CD8(+) T cell infiltration and affecting tumor regression.
Article
Physics, Fluids & Plasmas
C. Alex Safsten, Volodmyr Rybalko, Leonid Berlyand
Summary: This study focuses on the onset of motion of a living cell driven by myosin contraction. The results show that stable asymmetric moving states bifurcate from unstable radial stationary states, and these moving states have nonlinear asymptotic stability in modeling observable steady cell motion.
Article
Biochemistry & Molecular Biology
Binderiya Tserendavga, Noriyasu Ohshima, Chiaki Fujita, Koji Yuzawa, Mari Ohshima, Noriyuki Yanaka, Yoji Andrew Minamishima, Takashi Izumi
Summary: The study revealed that GDE7 can produce both LPA and cPA, while GDE4 only produces LPA. Both enzymes prefer 1-alkyllysophosphospholipids as substrates.
JOURNAL OF BIOCHEMISTRY
(2021)
Article
Cell Biology
Yan Liao, Lei Liu, Jiayao Yang, Zhaohong Shi
Summary: This study confirmed the existence of the autocrine pathway of lysophosphatidic acid (LPA) secretion regulated by autotaxin (ATX) in pancreatic cancer cells, and revealed the important role of the LPA/ATX axis in focal adhesion kinase (FAK) activation, cell proliferation, apoptosis, and motility.
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
(2022)
Review
Biochemistry & Molecular Biology
Razvan Borza, Fernando Salgado-Polo, Wouter H. Moolenaar, Anastassis Perrakis
Summary: This article reviews the structural features of ENPP1-7, aiming to understand how they have evolved to accommodate specific substrates and mediate different biological activities. The structural differences in the substrate-binding sites of ENPP members give each protein unique characteristics and explain their different functions in biology and pathophysiology.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ana Gomez-Larrauri, Patricia Gangoiti, Natalia Presa, Asier Dominguez-Herrera, Chiara Donati, Paola Bruni, Miguel Trueba, Antonio Gomez-Munoz, Alberto Ouro
Summary: Phosphatidic acid stimulates myoblast proliferation through interaction with LPA1 and LPA2 receptors, activating the PI3K/Akt and MEK/ERK1-2 pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Endocrinology & Metabolism
Yinlam Li, Li Jin, Yanquan Li, Jianing Qian, Zhengquan Wang, Xiaoguo Zheng, Chong Xie, Xuelian Zhang, Hefeng Huang, Yuchuan Zhou
Summary: This study reveals the involvement of LPA in regulating human sperm motility by enhancing glycolysis and activating L-type calcium channels. The findings shed new light on the understanding of the causes of asthenozoospermia and suggest that LPA could be used as a novel therapeutic agent to improve sperm function and fertilizing capacity.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Multidisciplinary Sciences
Chi Zhang, Weiyun Li, Xiaobo Lei, Zhenfei Xie, Linlin Qi, Hui Wang, Xia Xiao, Jun Xiao, Yuxiao Zheng, Chen Dong, Xin Zheng, Shiyang Chen, Jianfeng Chen, Bing Sun, Jun Qin, Qiwei Zhai, Jinsong Li, Bin Wei, Jianwei Wang, Hongyan Wang
Summary: The study reveals that in viral infection, LPA suppresses interferon production through the LPA1 receptor, affecting immune responses. Additionally, LPA1 and ROCK1/2 may impact viral infections by promoting vascular leaking or lung fibrosis. Therefore, targeting the LPA1-ROCK module could be beneficial for treating SARS-CoV-2 or other virus infections.
Review
Chemistry, Medicinal
Bhagyalalitha Meduri, Gurubasavaraj Veeranna Pujar, T. Durai Ananda Kumar, H. S. Akshatha, Arun Kumar Sethu, Manisha Singh, Abhinav Kanagarla, Bijo Mathew
Summary: Lysophosphatidic acid (LPA) and its receptors play crucial roles in cellular activities and are implicated in the pathogenesis of various diseases. Current research focuses on LPA receptors as new therapeutic targets for treating LPA-associated disorders.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Kaire Ojasalu, Sonja Lieber, Anna M. Sokol, Andrea Nist, Thorsten Stiewe, Imke Bullwinkel, Florian Finkernagel, Silke Reinartz, Sabine Mueller-Bruesselbach, Robert Grosse, Johannes Graumann, Rolf Mueller
Summary: Lysophosphatidic acid (LPA) species accumulate in the ascites of ovarian high-grade serous cancer (HGSC) and are associated with short relapse-free survival. LPA supports metastatic spread of cancer cells by activating multiple signaling pathways. However, a systematic analysis of the LPA-regulated signal transduction network in ovarian cancer cells has not been reported.
Article
Multidisciplinary Sciences
Ryohei Okasato, Kuniyuki Kano, Ryoji Kise, Asuka Inoue, Shigetomo Fukuhara, Junken Aoki
Summary: The study found that the ATX-LPA(6) axis cooperates with blood flow to generate contractile force in endothelial cells, contributing to the formation and maintenance of the CVP.
Review
Biochemistry & Molecular Biology
Shufan Jiang, Huili Yang, Mingqing Li
Summary: Lysophosphatidic acid (LPA) is a bioactive phospholipid that regulates various cell biological functions. Macrophages, present in most human tissues, play important roles in both physiology and pathology. The review highlights the significant role of LPA signaling in macrophages and its involvement in diseases such as inflammation-related diseases, cancer, atherosclerosis, and fibrosis. The therapeutic strategies targeting LPA are also discussed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Runchen Zhao, Siqi Cui, Zhuoxu Ge, Yuqi Zhang, Kaustav Bera, Lily Zhu, Sean X. Sun, Konstantinos Konstantopoulos
Summary: Cells transitioning from amoeboid to mesenchymal phenotypes in response to increasing hydraulic resistance exhibit oscillatory changes in actin network formation and focal adhesion maturation. Blocking the mechanosensor TRPM7 eliminates the dependence of transition period on resistance, and mathematical modeling reveals the role of intracellular calcium oscillations in this process. Hydraulic resistance emerges as a critical physical factor influencing cell phenotype, with a proposed framework for linking fluorescence signal fluctuations to morphological changes.