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• W1889312632 abstract "Cancer cells exhibit altered metabolism including aerobic glycolysis that channels several glycolytic intermediates into de novo purine biosynthetic pathway. We discovered increased expression of phosphoribosyl amidotransferase (PPAT) and phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) enzymes of de novo purine biosynthetic pathway in lung adenocarcinomas. Transcript analyses from next-generation RNA sequencing and gene expression profiling studies suggested that PPAT and PAICS can serve as prognostic biomarkers for aggressive lung adenocarcinoma. Immunohistochemical analysis of PAICS performed on tissue microarrays showed increased expression with disease progression and was significantly associated with poor prognosis. Through gene knockdown and over-expression studies we demonstrate that altering PPAT and PAICS expression modulates pyruvate kinase activity, cell proliferation and invasion. Furthermore we identified genomic amplification and aneuploidy of the divergently transcribed PPAT-PAICS genomic region in a subset of lung cancers. We also present evidence for regulation of both PPAT and PAICS and pyruvate kinase activity by L-glutamine, a co-substrate for PPAT. A glutamine antagonist, 6-Diazo-5-oxo-L-norleucine (DON) blocked glutamine mediated induction of PPAT and PAICS as well as reduced pyruvate kinase activity. In summary, this study reveals the regulatory mechanisms by which purine biosynthetic pathway enzymes PPAT and PAICS, and pyruvate kinase activity is increased and exposes an existing metabolic vulnerability in lung cancer cells that can be explored for pharmacological intervention." @default.
• W1889312632 created "2016-06-24" @default.
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• W1889312632 date "2015-06-23" @default.
• W1889312632 modified "2023-10-16" @default.
• W1889312632 title "Role and regulation of coordinately expressed<i>de novo</i>purine biosynthetic enzymes<i>PPAT</i>and<i>PAICS</i>in lung cancer" @default.
• W1889312632 cites W1540415768 @default.
• W1889312632 cites W1605420823 @default.
• W1889312632 cites W1663117206 @default.
• W1889312632 cites W1667881669 @default.
• W1889312632 cites W1745549119 @default.
• W1889312632 cites W1775259416 @default.
• W1889312632 cites W1892496998 @default.
• W1889312632 cites W1967362499 @default.
• W1889312632 cites W1968065996 @default.
• W1889312632 cites W1968315432 @default.
• W1889312632 cites W1968510406 @default.
• W1889312632 cites W1973304708 @default.
• W1889312632 cites W1974720903 @default.
• W1889312632 cites W1979843175 @default.
• W1889312632 cites W1980121152 @default.
• W1889312632 cites W1988078905 @default.
• W1889312632 cites W1996646041 @default.
• W1889312632 cites W2000630389 @default.
• W1889312632 cites W2000771269 @default.
• W1889312632 cites W2002575472 @default.
• W1889312632 cites W2002765383 @default.
• W1889312632 cites W2008699255 @default.
• W1889312632 cites W2022323055 @default.
• W1889312632 cites W2029195626 @default.
• W1889312632 cites W2034530633 @default.
• W1889312632 cites W2038623184 @default.
• W1889312632 cites W2044545697 @default.
• W1889312632 cites W2046759180 @default.
• W1889312632 cites W2049923433 @default.
• W1889312632 cites W2050079849 @default.
• W1889312632 cites W2051886524 @default.
• W1889312632 cites W2056174640 @default.
• W1889312632 cites W2058451329 @default.
• W1889312632 cites W2065746026 @default.
• W1889312632 cites W2069269337 @default.
• W1889312632 cites W2070544303 @default.
• W1889312632 cites W2071373243 @default.
• W1889312632 cites W2071480068 @default.
• W1889312632 cites W2076562742 @default.
• W1889312632 cites W2080903186 @default.
• W1889312632 cites W2082668371 @default.
• W1889312632 cites W2086816631 @default.
• W1889312632 cites W2090029719 @default.
• W1889312632 cites W2090406819 @default.
• W1889312632 cites W2091607700 @default.
• W1889312632 cites W2092527265 @default.
• W1889312632 cites W2093775484 @default.
• W1889312632 cites W2094576137 @default.
• W1889312632 cites W2094957481 @default.
• W1889312632 cites W2095987251 @default.
• W1889312632 cites W2097259163 @default.
• W1889312632 cites W2099755355 @default.
• W1889312632 cites W2104830962 @default.
• W1889312632 cites W2114843025 @default.
• W1889312632 cites W2116201681 @default.
• W1889312632 cites W2117692326 @default.
• W1889312632 cites W2121691257 @default.
• W1889312632 cites W2132165198 @default.
• W1889312632 cites W2134847995 @default.
• W1889312632 cites W2141082830 @default.
• W1889312632 cites W2142748510 @default.
• W1889312632 cites W2149441684 @default.
• W1889312632 cites W2151499633 @default.
• W1889312632 cites W2154678665 @default.
• W1889312632 cites W2155354546 @default.
• W1889312632 cites W2155680682 @default.
• W1889312632 cites W2155888371 @default.
• W1889312632 cites W2157760261 @default.
• W1889312632 cites W2162102103 @default.
• W1889312632 cites W2165831518 @default.
• W1889312632 cites W2167972473 @default.
• W1889312632 cites W2170552969 @default.
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• W1889312632 doi "https://doi.org/10.18632/oncotarget.4352" @default.
• W1889312632 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4695129" @default.
• W1889312632 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26140362" @default.
• W1889312632 hasPublicationYear "2015" @default.
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