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Open AccessArticle

Hypoxia Downregulates LPP3 and Promotes the Spatial Segregation of ATX and LPP1 During Cancer Cell Invasion

Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec, QC J1H 5N4, Canada
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Cancers 2019, 11(9), 1403; https://doi.org/10.3390/cancers11091403
Received: 9 August 2019 / Revised: 7 September 2019 / Accepted: 12 September 2019 / Published: 19 September 2019
(This article belongs to the Special Issue Lysophosphatidic Acid Signalling in Cancer)
Hypoxia is a common characteristic of advanced solid tumors and a potent driver of tumor invasion and metastasis. Recent evidence suggests the involvement of autotaxin (ATX) and lysophosphatidic acid receptors (LPARs) in cancer cell invasion promoted by the hypoxic tumor microenvironment; however, the transcriptional and/or spatiotemporal control of this process remain unexplored. Herein, we investigated whether hypoxia promotes cell invasion by affecting the main enzymes involved in its production (ATX) and degradation (lipid phosphate phosphatases, LPP1 and LPP3). We report that hypoxia not only modulates the expression levels of lysophosphatidic acid (LPA) regulatory enzymes but also induces their significant spatial segregation in a variety of cancers. While LPP3 expression was downregulated by hypoxia, ATX and LPP1 were asymmetrically redistributed to the leading edge and to the trailing edge, respectively. This was associated with the opposing roles of ATX and LPPs in cell invasion. The regulated expression and compartmentalization of these enzymes of opposing function can provide an effective way to control the generation of an LPA gradient that drives cellular invasion and migration in the hypoxic zones of tumors. View Full-Text
Keywords: hypoxia; autotaxin; ATX; LPA; lipid phosphate phosphatases; LPP1; LPP3; cell invasion; invadopodia hypoxia; autotaxin; ATX; LPA; lipid phosphate phosphatases; LPP1; LPP3; cell invasion; invadopodia
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MDPI and ACS Style

Harper, K.; Brochu-Gaudreau, K.; Saucier, C.; Dubois, C.M. Hypoxia Downregulates LPP3 and Promotes the Spatial Segregation of ATX and LPP1 During Cancer Cell Invasion. Cancers 2019, 11, 1403.

AMA Style

Harper K, Brochu-Gaudreau K, Saucier C, Dubois CM. Hypoxia Downregulates LPP3 and Promotes the Spatial Segregation of ATX and LPP1 During Cancer Cell Invasion. Cancers. 2019; 11(9):1403.

Chicago/Turabian Style

Harper, Kelly; Brochu-Gaudreau, Karine; Saucier, Caroline; Dubois, Claire M. 2019. "Hypoxia Downregulates LPP3 and Promotes the Spatial Segregation of ATX and LPP1 During Cancer Cell Invasion" Cancers 11, no. 9: 1403.

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