Phosphatase-resistant analogues of lysophosphatidic acid: Agonists promote healing, antagonists and autotaxin inhibitors treat cancer

Glenn D. Prestwich; Joanna Gajewiak; Honglu Zhang; Xiaoyu Xu; Guanghui Yang; Monica Serban

doi:10.1016/j.bbalip.2008.03.008

Phosphatase-resistant analogues of lysophosphatidic acid: Agonists promote healing, antagonists and autotaxin inhibitors treat cancer

Glenn D. Prestwich
, Joanna Gajewiak
, Honglu Zhang
, Xiaoyu Xu
, Guanghui Yang
, Monica Serban

University of Utah

Research output: Contribution to journal › Review article › peer-review

68 Scopus citations

Abstract

Isoform-selective agonists and antagonists of the lysophosphatidic acid (LPA) G protein-coupled receptors (GPCRs) have important potential applications in cell biology and therapy. LPA GPCRs regulate cancer cell proliferation, invasion, angiogenesis, and also biochemical resistance to chemotherapy- and radiotherapy-induced apoptosis. LPA and its analogues also are feedback inhibitors of the enzyme lysophospholipase D (lysoPLD, a.k.a., autotaxin, ATX), a central regulator of invasion and metastasis. For cancer therapy, the optimal therapeutic profile would be a metabolically-stabilized, pan-LPA receptor antagonist that also inhibited lysoPLD. For protection of gastrointestinal mucosa and lymphocytes, LPA agonists would be desirable to minimize or reverse radiation or chemical-induced injury. Analogues of lysophosphatidic acid (LPA) that are chemically modified to be less susceptible to phospholipases and phosphatases show activity as long-lived receptor-specific agonists and antagonists for LPA receptors, as well as inhibitors for the lysoPLD activity of ATX.

Original language	English
Pages (from-to)	588-594
Number of pages	7
Journal	Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume	1781
Issue number	9
DOIs	https://doi.org/10.1016/j.bbalip.2008.03.008
State	Published - Sep 2008

Funding

We thank the National Institutes of Health for grant NS29632 to G.D.P. We also thank our colleagues, G. Tigyi (U Tennessee, Memphis), J. Aoki (U Tokyo), A. Parrill (U Memphis), M. Murph and G. B. Mills (M. D. Anderson Cancer Center) for ongoing collaborative studies on biological activity in literature cited herein, and S. W. Nam (Catholic U, Korea) for providing the NIH 3T3 ras ATX cell line.

Funder number
R01NS029632

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Aminooxy
Autotaxin
GPCR antagonist
Lysophospholipase D inhibitor
Methylene phosphonate
Phosphorothioate
Receptor isoform selectivity
Tumor regression

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10.1016/j.bbalip.2008.03.008

Cite this

@article{b320d078b43340d28ac751a2b099dd0f,

title = "Phosphatase-resistant analogues of lysophosphatidic acid: Agonists promote healing, antagonists and autotaxin inhibitors treat cancer",

abstract = "Isoform-selective agonists and antagonists of the lysophosphatidic acid (LPA) G protein-coupled receptors (GPCRs) have important potential applications in cell biology and therapy. LPA GPCRs regulate cancer cell proliferation, invasion, angiogenesis, and also biochemical resistance to chemotherapy- and radiotherapy-induced apoptosis. LPA and its analogues also are feedback inhibitors of the enzyme lysophospholipase D (lysoPLD, a.k.a., autotaxin, ATX), a central regulator of invasion and metastasis. For cancer therapy, the optimal therapeutic profile would be a metabolically-stabilized, pan-LPA receptor antagonist that also inhibited lysoPLD. For protection of gastrointestinal mucosa and lymphocytes, LPA agonists would be desirable to minimize or reverse radiation or chemical-induced injury. Analogues of lysophosphatidic acid (LPA) that are chemically modified to be less susceptible to phospholipases and phosphatases show activity as long-lived receptor-specific agonists and antagonists for LPA receptors, as well as inhibitors for the lysoPLD activity of ATX.",

keywords = "Aminooxy, Autotaxin, GPCR antagonist, Lysophospholipase D inhibitor, Methylene phosphonate, Phosphorothioate, Receptor isoform selectivity, Tumor regression",

author = "Prestwich, \{Glenn D.\} and Joanna Gajewiak and Honglu Zhang and Xiaoyu Xu and Guanghui Yang and Monica Serban",

note = "Funding Information: We thank the National Institutes of Health for grant NS29632 to G.D.P. We also thank our colleagues, G. Tigyi (U Tennessee, Memphis), J. Aoki (U Tokyo), A. Parrill (U Memphis), M. Murph and G. B. Mills (M. D. Anderson Cancer Center) for ongoing collaborative studies on biological activity in literature cited herein, and S. W. Nam (Catholic U, Korea) for providing the NIH 3T3 ras ATX cell line.",

year = "2008",

month = sep,

doi = "10.1016/j.bbalip.2008.03.008",

language = "English",

volume = "1781",

pages = "588--594",

journal = "Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids",

issn = "1388-1981",

publisher = "Elsevier B.V.",

number = "9",

}

Phosphatase-resistant analogues of lysophosphatidic acid: Agonists promote healing, antagonists and autotaxin inhibitors treat cancer. / Prestwich, Glenn D.; Gajewiak, Joanna; Zhang, Honglu et al.
In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, Vol. 1781, No. 9, 09.2008, p. 588-594.

Research output: Contribution to journal › Review article › peer-review

TY - JOUR

T1 - Phosphatase-resistant analogues of lysophosphatidic acid

T2 - Agonists promote healing, antagonists and autotaxin inhibitors treat cancer

AU - Prestwich, Glenn D.

AU - Gajewiak, Joanna

AU - Zhang, Honglu

AU - Xu, Xiaoyu

AU - Yang, Guanghui

AU - Serban, Monica

N1 - Funding Information: We thank the National Institutes of Health for grant NS29632 to G.D.P. We also thank our colleagues, G. Tigyi (U Tennessee, Memphis), J. Aoki (U Tokyo), A. Parrill (U Memphis), M. Murph and G. B. Mills (M. D. Anderson Cancer Center) for ongoing collaborative studies on biological activity in literature cited herein, and S. W. Nam (Catholic U, Korea) for providing the NIH 3T3 ras ATX cell line.

PY - 2008/9

Y1 - 2008/9

N2 - Isoform-selective agonists and antagonists of the lysophosphatidic acid (LPA) G protein-coupled receptors (GPCRs) have important potential applications in cell biology and therapy. LPA GPCRs regulate cancer cell proliferation, invasion, angiogenesis, and also biochemical resistance to chemotherapy- and radiotherapy-induced apoptosis. LPA and its analogues also are feedback inhibitors of the enzyme lysophospholipase D (lysoPLD, a.k.a., autotaxin, ATX), a central regulator of invasion and metastasis. For cancer therapy, the optimal therapeutic profile would be a metabolically-stabilized, pan-LPA receptor antagonist that also inhibited lysoPLD. For protection of gastrointestinal mucosa and lymphocytes, LPA agonists would be desirable to minimize or reverse radiation or chemical-induced injury. Analogues of lysophosphatidic acid (LPA) that are chemically modified to be less susceptible to phospholipases and phosphatases show activity as long-lived receptor-specific agonists and antagonists for LPA receptors, as well as inhibitors for the lysoPLD activity of ATX.

AB - Isoform-selective agonists and antagonists of the lysophosphatidic acid (LPA) G protein-coupled receptors (GPCRs) have important potential applications in cell biology and therapy. LPA GPCRs regulate cancer cell proliferation, invasion, angiogenesis, and also biochemical resistance to chemotherapy- and radiotherapy-induced apoptosis. LPA and its analogues also are feedback inhibitors of the enzyme lysophospholipase D (lysoPLD, a.k.a., autotaxin, ATX), a central regulator of invasion and metastasis. For cancer therapy, the optimal therapeutic profile would be a metabolically-stabilized, pan-LPA receptor antagonist that also inhibited lysoPLD. For protection of gastrointestinal mucosa and lymphocytes, LPA agonists would be desirable to minimize or reverse radiation or chemical-induced injury. Analogues of lysophosphatidic acid (LPA) that are chemically modified to be less susceptible to phospholipases and phosphatases show activity as long-lived receptor-specific agonists and antagonists for LPA receptors, as well as inhibitors for the lysoPLD activity of ATX.

KW - Aminooxy

KW - Autotaxin

KW - GPCR antagonist

KW - Lysophospholipase D inhibitor

KW - Methylene phosphonate

KW - Phosphorothioate

KW - Receptor isoform selectivity

KW - Tumor regression

UR - https://www.scopus.com/pages/publications/49949105271

U2 - 10.1016/j.bbalip.2008.03.008

DO - 10.1016/j.bbalip.2008.03.008

M3 - Review article

C2 - 18454946

AN - SCOPUS:49949105271

SN - 1388-1981

VL - 1781

SP - 588

EP - 594

JO - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

JF - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

IS - 9

ER -

Phosphatase-resistant analogues of lysophosphatidic acid: Agonists promote healing, antagonists and autotaxin inhibitors treat cancer

Abstract

Funding

UN SDGs

Keywords

Access to Document

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