Suppression of Membranous LRP5 Recycling, Wnt/β-Catenin Signaling, and Colon Carcinogenesis by 15-LOX-1 Peroxidation of Linoleic Acid in PI3P

Fuyao Liu; Xiangsheng Zuo; Yi Liu; Yasunori Deguchi; Micheline J. Moussalli; Weidong Chen; Peiying Yang; Bo Wei; Lin Tan; Philip L. Lorenzi; Shen Gao; Jonathan C. Jaoude; Amir Mehdizadeh; Lovie Ann Valentin; Daoyan Wei; Imad Shureiqi

doi:10.1016/j.celrep.2020.108049

Suppression of Membranous LRP5 Recycling, Wnt/β-Catenin Signaling, and Colon Carcinogenesis by 15-LOX-1 Peroxidation of Linoleic Acid in PI3P

Fuyao Liu, Xiangsheng Zuo, Yi Liu, Yasunori Deguchi, Micheline J. Moussalli, Weidong Chen, Peiying Yang, Bo Wei, Lin Tan, Philip L. Lorenzi, Shen Gao, Jonathan C. Jaoude, Amir Mehdizadeh, Lovie Ann Valentin, Daoyan Wei, Imad Shureiqi

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

APC mutation activation of Wnt/β-catenin drives initiation of colorectal carcinogenesis (CRC). Additional factors potentiate β-catenin activation to promote CRC. Western diets are enriched in linoleic acid (LA); LA-enriched diets promote chemically induced CRC in rodents. 15-Lipoxygenase-1 (15-LOX-1), the main LA-metabolizing enzyme, is transcriptionally silenced during CRC. Whether LA and 15-LOX-1 affect Wnt/β-catenin signaling is unclear. We report that high dietary LA promotes CRC in mice treated with azoxymethane or with an intestinally targeted Apc mutation (Apc^Δ580) by upregulating Wnt receptor LRP5 protein expression and β-catenin activation. 15-LOX-1 transgenic expression in mouse intestinal epithelial cells suppresses LRP5 protein expression, β-catenin activation, and CRC. 15-LOX-1 peroxidation of LA in phosphatidylinositol-3-phosphates (PI3P_LA) leads to PI3P_13-HODE formation, which decreases PI3P binding to SNX17 and LRP5 and inhibits LRP5 recycling from endosomes to the plasma membrane, thereby increasing LRP5 lysosomal degradation. This regulatory mechanism of LRP5/Wnt/β-catenin signaling could be therapeutically targeted to suppress CRC.

Original language	English (US)
Article number	108049
Journal	Cell Reports
Volume	32
Issue number	7
DOIs	https://doi.org/10.1016/j.celrep.2020.108049
State	Published - Aug 18 2020

Keywords

13-HODE
15-LOX-1
LRP5
colorectal cancer
linoleic acid
phosphatidylinositol-3-phosphate
sorting nexin 17 (SNX17)
β-catenin

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

MD Anderson CCSG core facilities

Advanced Technology Genomics Core
Flow Cytometry and Cellular Imaging Facility
Functional Genomics Core
Genetically Engineered Mouse Facility
Metabolomics Facility
Research Animal Support Facility
Tissue Biospecimen and Pathology Resource
Cytogenetics and Cell Authentication Core
Laboratory Animal Genetic Services
Bioinformatics Shared Resource

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10.1016/j.celrep.2020.108049

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Liu, F., Zuo, X., Liu, Y., Deguchi, Y., Moussalli, M. J., Chen, W., Yang, P., Wei, B., Tan, L., Lorenzi, P. L., Gao, S., Jaoude, J. C., Mehdizadeh, A., Valentin, L. A., Wei, D., & Shureiqi, I. (2020). Suppression of Membranous LRP5 Recycling, Wnt/β-Catenin Signaling, and Colon Carcinogenesis by 15-LOX-1 Peroxidation of Linoleic Acid in PI3P. Cell Reports, 32(7), Article 108049. https://doi.org/10.1016/j.celrep.2020.108049

Liu, F, Zuo, X , Liu, Y, Deguchi, Y, Moussalli, MJ, Chen, W, Yang, P , Wei, B , Tan, L , Lorenzi, PL, Gao, S, Jaoude, JC, Mehdizadeh, A, Valentin, LA, Wei, D & Shureiqi, I 2020, 'Suppression of Membranous LRP5 Recycling, Wnt/β-Catenin Signaling, and Colon Carcinogenesis by 15-LOX-1 Peroxidation of Linoleic Acid in PI3P', Cell Reports, vol. 32, no. 7, 108049. https://doi.org/10.1016/j.celrep.2020.108049

@article{f204fe70437145d0b756a38f47f19122,

title = "Suppression of Membranous LRP5 Recycling, Wnt/β-Catenin Signaling, and Colon Carcinogenesis by 15-LOX-1 Peroxidation of Linoleic Acid in PI3P",

abstract = "APC mutation activation of Wnt/β-catenin drives initiation of colorectal carcinogenesis (CRC). Additional factors potentiate β-catenin activation to promote CRC. Western diets are enriched in linoleic acid (LA); LA-enriched diets promote chemically induced CRC in rodents. 15-Lipoxygenase-1 (15-LOX-1), the main LA-metabolizing enzyme, is transcriptionally silenced during CRC. Whether LA and 15-LOX-1 affect Wnt/β-catenin signaling is unclear. We report that high dietary LA promotes CRC in mice treated with azoxymethane or with an intestinally targeted Apc mutation (ApcΔ580) by upregulating Wnt receptor LRP5 protein expression and β-catenin activation. 15-LOX-1 transgenic expression in mouse intestinal epithelial cells suppresses LRP5 protein expression, β-catenin activation, and CRC. 15-LOX-1 peroxidation of LA in phosphatidylinositol-3-phosphates (PI3P_LA) leads to PI3P_13-HODE formation, which decreases PI3P binding to SNX17 and LRP5 and inhibits LRP5 recycling from endosomes to the plasma membrane, thereby increasing LRP5 lysosomal degradation. This regulatory mechanism of LRP5/Wnt/β-catenin signaling could be therapeutically targeted to suppress CRC.",

keywords = "13-HODE, 15-LOX-1, LRP5, colorectal cancer, linoleic acid, phosphatidylinositol-3-phosphate, sorting nexin 17 (SNX17), β-catenin",

author = "Fuyao Liu and Xiangsheng Zuo and Yi Liu and Yasunori Deguchi and Moussalli, {Micheline J.} and Weidong Chen and Peiying Yang and Bo Wei and Lin Tan and Lorenzi, {Philip L.} and Shen Gao and Jaoude, {Jonathan C.} and Amir Mehdizadeh and Valentin, {Lovie Ann} and Daoyan Wei and Imad Shureiqi",

note = "Funding Information: This work was supported by the National Cancer Institute ( R01-CA195686 and R01-CA206539 to I.S.) and the Cancer Prevention and Research Institute of Texas ( RP150195 to I.S.). This study made use of the MD Anderson Cancer Center Genetically Engineered Mouse Facility, Functional Genomics Core, Flow Cytometry and Cellular Imaging Facility, Sequencing and Microarray Facility, and Research Animal Support Facility—Smithville Laboratory Animal Genetic Services, supported by Cancer Center Support Grant P30CA016672 , and the MD Anderson Cancer Center metabolomics facility service, supported in part by Cancer Prevention and Research Institute of Texas grant RP130397 and National Institutes of Health grant 1S10OD012304-01 . We thank Dr. Jae-Il Park at The University of Texas MD Anderson Cancer Center for his feedback on this work. We thank Ms. Sarah J. Bronson and Ms. Erica Goodoff in Scientific Publications, Research Medical Library at MD Anderson for editing the article. We thank Dr. Matthew Warman in Boston Children{\textquoteright}s Hospital for donating the LRP5 plasmid. Publisher Copyright: {\textcopyright} 2020 The Authors",

year = "2020",

month = aug,

day = "18",

doi = "10.1016/j.celrep.2020.108049",

language = "English (US)",

volume = "32",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "7",

}

TY - JOUR

T1 - Suppression of Membranous LRP5 Recycling, Wnt/β-Catenin Signaling, and Colon Carcinogenesis by 15-LOX-1 Peroxidation of Linoleic Acid in PI3P

AU - Liu, Fuyao

AU - Zuo, Xiangsheng

AU - Liu, Yi

AU - Deguchi, Yasunori

AU - Moussalli, Micheline J.

AU - Chen, Weidong

AU - Yang, Peiying

AU - Wei, Bo

AU - Tan, Lin

AU - Lorenzi, Philip L.

AU - Gao, Shen

AU - Jaoude, Jonathan C.

AU - Mehdizadeh, Amir

AU - Valentin, Lovie Ann

AU - Wei, Daoyan

AU - Shureiqi, Imad

N1 - Funding Information: This work was supported by the National Cancer Institute ( R01-CA195686 and R01-CA206539 to I.S.) and the Cancer Prevention and Research Institute of Texas ( RP150195 to I.S.). This study made use of the MD Anderson Cancer Center Genetically Engineered Mouse Facility, Functional Genomics Core, Flow Cytometry and Cellular Imaging Facility, Sequencing and Microarray Facility, and Research Animal Support Facility—Smithville Laboratory Animal Genetic Services, supported by Cancer Center Support Grant P30CA016672 , and the MD Anderson Cancer Center metabolomics facility service, supported in part by Cancer Prevention and Research Institute of Texas grant RP130397 and National Institutes of Health grant 1S10OD012304-01 . We thank Dr. Jae-Il Park at The University of Texas MD Anderson Cancer Center for his feedback on this work. We thank Ms. Sarah J. Bronson and Ms. Erica Goodoff in Scientific Publications, Research Medical Library at MD Anderson for editing the article. We thank Dr. Matthew Warman in Boston Children’s Hospital for donating the LRP5 plasmid. Publisher Copyright: © 2020 The Authors

PY - 2020/8/18

Y1 - 2020/8/18

N2 - APC mutation activation of Wnt/β-catenin drives initiation of colorectal carcinogenesis (CRC). Additional factors potentiate β-catenin activation to promote CRC. Western diets are enriched in linoleic acid (LA); LA-enriched diets promote chemically induced CRC in rodents. 15-Lipoxygenase-1 (15-LOX-1), the main LA-metabolizing enzyme, is transcriptionally silenced during CRC. Whether LA and 15-LOX-1 affect Wnt/β-catenin signaling is unclear. We report that high dietary LA promotes CRC in mice treated with azoxymethane or with an intestinally targeted Apc mutation (ApcΔ580) by upregulating Wnt receptor LRP5 protein expression and β-catenin activation. 15-LOX-1 transgenic expression in mouse intestinal epithelial cells suppresses LRP5 protein expression, β-catenin activation, and CRC. 15-LOX-1 peroxidation of LA in phosphatidylinositol-3-phosphates (PI3P_LA) leads to PI3P_13-HODE formation, which decreases PI3P binding to SNX17 and LRP5 and inhibits LRP5 recycling from endosomes to the plasma membrane, thereby increasing LRP5 lysosomal degradation. This regulatory mechanism of LRP5/Wnt/β-catenin signaling could be therapeutically targeted to suppress CRC.

AB - APC mutation activation of Wnt/β-catenin drives initiation of colorectal carcinogenesis (CRC). Additional factors potentiate β-catenin activation to promote CRC. Western diets are enriched in linoleic acid (LA); LA-enriched diets promote chemically induced CRC in rodents. 15-Lipoxygenase-1 (15-LOX-1), the main LA-metabolizing enzyme, is transcriptionally silenced during CRC. Whether LA and 15-LOX-1 affect Wnt/β-catenin signaling is unclear. We report that high dietary LA promotes CRC in mice treated with azoxymethane or with an intestinally targeted Apc mutation (ApcΔ580) by upregulating Wnt receptor LRP5 protein expression and β-catenin activation. 15-LOX-1 transgenic expression in mouse intestinal epithelial cells suppresses LRP5 protein expression, β-catenin activation, and CRC. 15-LOX-1 peroxidation of LA in phosphatidylinositol-3-phosphates (PI3P_LA) leads to PI3P_13-HODE formation, which decreases PI3P binding to SNX17 and LRP5 and inhibits LRP5 recycling from endosomes to the plasma membrane, thereby increasing LRP5 lysosomal degradation. This regulatory mechanism of LRP5/Wnt/β-catenin signaling could be therapeutically targeted to suppress CRC.

KW - 13-HODE

KW - 15-LOX-1

KW - LRP5

KW - colorectal cancer

KW - linoleic acid

KW - phosphatidylinositol-3-phosphate

KW - sorting nexin 17 (SNX17)

KW - β-catenin

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UR - http://www.scopus.com/inward/citedby.url?scp=85089488132&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2020.108049

DO - 10.1016/j.celrep.2020.108049

M3 - Article

C2 - 32814052

AN - SCOPUS:85089488132

SN - 2211-1247

VL - 32

JO - Cell Reports

JF - Cell Reports

IS - 7

M1 - 108049

ER -

Suppression of Membranous LRP5 Recycling, Wnt/β-Catenin Signaling, and Colon Carcinogenesis by 15-LOX-1 Peroxidation of Linoleic Acid in PI3P

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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