Adenylosuccinate lyase enhances aggressiveness of endometrial cancer by increasing killer cell lectin-like receptor C3 expression by fumarate.

Laboratory Investigation; a Journal of Technical Methods and Pathology
Haengki ParkEiichi Morii

Abstract

Adenylosuccinate lyase (ADSL) is an enzyme that plays important roles in de novo purine synthesis. Although ADSL was reported to be upregulated in various malignancies, such as colorectal, breast, and prostate cancer, as well as gliomas, the mechanism by which elevated ADSL expression contributes to cancer has not been elucidated. We previously performed a shotgun proteomics analysis to characterize specific proteins associated with the properties of the aldehyde dehydrogenase (ALDH)-high cell population, which was reported to be involved in tumorigenic potential, and showed that ADSL expression is upregulated in the ALDH-high population of endometrial cancer. Here, we showed that ADSL is involved in endometrial cancer aggressiveness by regulating expression of killer cell lectin-like receptor C3 (KLRC3), which is a receptor expressed on natural killer cells. Immunohistochemical analysis indicated that ADSL expression increased as endometrioid carcinoma specimens became more poorly differentiated and higher degree of primary tumor progression. Knockdown of ADSL in endometrial cancer cells decreased cell proliferation, migration, and invasive capability, and caused the cells to adopt a more rounded shape. DNA microarray analysis...Continue Reading

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Citations

Nov 20, 2020·Experimental Cell Research·Kristopher MontroseJuha Saarikangas
May 25, 2021·Frontiers in Chemistry·Di ZhouJingchao Lin
Dec 19, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tingting JiangWen Xue
Dec 9, 2020·Seminars in Cancer Biology·Claudia PeitzschAnna Dubrovska

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Datasets Mentioned

BETA
GSE100703

Methods Mentioned

BETA
flow cytometry
transfection
electrophoresis
PCR
Assay
scraping
FACS

Software Mentioned

Excel
Subio Basic Plug - in
Subio Platform
Image J
JMP Pro

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