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

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, t...

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Bibliographic Details
Published in:Cancers 2019-09, Vol.11 (9), p.1403
Main Authors: Harper, Kelly, Brochu-Gaudreau, Karine, Saucier, Caroline, Dubois, Claire
Format: Article
Language:English
Subjects:
Brain cancer
Breast cancer
Enzymes
Gene expression
Hypoxia
Kinases
Lipids
Localization
Lysophosphatidic acid
Lysophosphatidic acid receptors
Medical prognosis
Melanoma
Metabolism
Metastases
Metastasis
Motility
Ovarian cancer
Patients
Protein expression
Proteins
Sarcoma
Solid tumors
Transcription
Tumor microenvironment
Tumorigenesis
Tumors
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Summary: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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers11091403