SphK2 confers 5-fluorouracil resistance to colorectal cancer via upregulating H3K56ac-mediated DPD expression

Aberrant sphingolipid metabolism has been implicated in chemoresistance, but the underlying mechanisms are still poorly understood. Herein we revealed a previously unrecognized mechanism of 5-fluorouracil (5-FU) resistance contributed by high SphK2-upregulated dihydropyrimidine dehydrogenase (DPD) i...

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Veröffentlicht in:	Oncogene 2020-07, Vol.39 (29), p.5214-5227
Hauptverfasser:	Zhang, Yu-Hang, Shi, Wen-Na, Wu, Shu-Hua, Miao, Rong-Rong, Sun, Shi-Yue, Luo, Dong-Dong, Wan, Sheng-Biao, Guo, Zhi-Kun, Wang, Wen-Yu, Yu, Xin-Feng, Cui, Shu-Xiang, Qu, Xian-Jun
Format:	Artikel
Sprache:	eng
Schlagworte:	101/47 13/1 13/105 13/109 5-Fluorouracil 59/5 631/154/155 631/67/1059/2326 631/67/1504/1885 64/60 82/58 82/80 Alanine Analysis Animal models Animals Apoptosis Cancer Cell Biology Cell culture Chemoresistance Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - genetics Colorectal Neoplasms - pathology Dihydrouracil Dehydrogenase (NADP) - metabolism Drug Resistance, Neoplasm - genetics Fluorouracil Fluorouracil - pharmacology Fluorouracil - therapeutic use Human Genetics Humans Internal Medicine Lipid metabolism Medicine Medicine & Public Health Mice Oncology Phosphotransferases (Alcohol Group Acceptor) - metabolism Reporter gene Tumor cell lines Tumors Up-Regulation Xenografts
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Zusammenfassung:	Aberrant sphingolipid metabolism has been implicated in chemoresistance, but the underlying mechanisms are still poorly understood. Herein we revealed a previously unrecognized mechanism of 5-fluorouracil (5-FU) resistance contributed by high SphK2-upregulated dihydropyrimidine dehydrogenase (DPD) in colorectal cancer (CRC), which is evidenced from human CRC specimens, animal models, and cancer cell lines. TMA samples from randomly selected 60 CRC specimens firstly identified the clinical correlation between high SphK2 and increased DPD ( p
ISSN:	0950-9232 1476-5594
DOI:	10.1038/s41388-020-1352-y