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Integrated omics-analysis reveals Wnt-mediated NAD(+) metabolic reprogramming in cancer stem-like cells

Title
Integrated omics-analysis reveals Wnt-mediated NAD(+) metabolic reprogramming in cancer stem-like cells
Authors
Lee, JueunKee, Hyun JungMin, SoonkiPark, Ki CheongPark, SunhoHwang, Tae HyunRyu, Do HyunHwang, Geum-SookCheong, Jae-Ho
Ewha Authors
황금숙
SCOPUS Author ID
황금숙scopusscopus
Issue Date
2016
Journal Title
ONCOTARGET
ISSN
1949-2553JCR Link
Citation
vol. 7, no. 30, pp. 48562 - 48576
Keywords
calcium signalingcancer stem cellsintegrated analysismetabolic reprogrammingWnt signaling
Publisher
IMPACT JOURNALS LLC
Indexed
SCIE; SCOPUS WOS scopus
Abstract
Abnormal tumor cell metabolism is a consequence of alterations in signaling pathways that provide critical selective advantage to cancer cells. However, a systematic characterization of the metabolic and signaling pathways altered in cancer stem-like cells (CSCs) is currently lacking. Using nuclear magnetic resonance and mass spectrometry, we profiled the whole-cell metabolites of a pair of parental (P-231) and stem-like cancer cells (S-231), and then integrated with whole transcriptome profiles. We identified elevated NAAD(+) in S-231 along with a coordinated increased expression of genes in Wnt/calcium signaling pathway, reflecting the correlation between metabolic reprogramming and altered signaling pathways. The expression of CD38 and ALP, upstream NAAD(+) regulatory enzymes, was oppositely regulated between P-and S-231; high CD38 strongly correlated with NAADP in P-231 while high ALP with NAAD(+) levels in S-231. Antagonizing Wnt activity by dnTCF4 transfection reversed the levels of NAAD(+) and ALP expression in S-231. Of note, elevated NAAD(+) caused a decrease of cytosolic Ca2+ levels preventing calcium-induced apoptosis in nutrient-deprived conditions. Reprograming of NAD(+) metabolic pathway instigated by Wnt signaling prevented cytosolic Ca2+ overload thereby inhibiting calcium-induced apoptosis in S-231. These results suggest that "oncometabolites" resulting from cross talk between the deranged core cancer signaling pathway and metabolic network provide a selective advantage to CSCs.
DOI
10.18632/oncotarget.10432
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자연과학대학 > 화학·나노과학전공 > Journal papers
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