APM OpenIR
cMyc-mediated activation of serine biosynthesis pathway is critical for cancer progression under nutrient deprivation conditions
Sun Linchong1; Song Libing2; Wan Qianfen3; Wu Gongwei1; Li Xinghua2; Wang Yinghui1; Wang Jin3; Liu Zhaoji1; Zhong Xiuying1; He Xiaoping1; Shen Shengqi1; Pan Xin4; Li Ailing4; Wang Yulan3; Gao Ping1; Tang Huiru3; Zhang Huafeng1
2015
Source PublicationCell Research
ISSN1001-0602
Volume25Issue:4Pages:429
AbstractCancer cells are known to undergo metabolic reprogramming to sustain survival and rapid proliferation, however, it remains to be fully elucidated how oncogenic lesions coordinate the metabolic switch under various stressed conditions. Here we show that deprivation of glucose or glutamine, two major nutrition sources for cancer cells, dramatically activated serine biosynthesis pathway (SSP) that was accompanied by elevated cMyc expression. We further identified that cMyc stimulated SSP activation by transcriptionally upregulating expression of multiple SSP enzymes. Moreover, we demonstrated that SSP activation facilitated by cMyc led to elevated glutathione (GSH) production, cell cycle progression and nucleic acid synthesis, which are essential for cell survival and proliferation especially under nutrient-deprived conditions. We further uncovered that phosphoserine phosphatase (PSPH), the final rate-limiting enzyme of the SSP pathway, is critical for cMyc-driven cancer progression both in vitro and in vivo , and importantly, aberrant expression of PSPH is highly correlated with mortality in hepatocellular carcinoma (HCC) patients, suggesting a potential causal relation between this cMyc-regulated enzyme, or SSP activation in general, and cancer development. Taken together, our results reveal that aberrant expression of cMyc leads to the enhanced SSP activation, an essential part of metabolic switch, to facilitate cancer progression under nutrient-deprived conditions.
Language英语
Document Type期刊论文
Identifierhttp://ir.apm.ac.cn/handle/112942/18547
Collection中国科学院武汉物理与数学研究所
Affiliation1.中国科学技术大学
2.中山大学
3.中国科学院武汉物理与数学研究所
4.China National Center of Biomedical Analysis
Recommended Citation
GB/T 7714
Sun Linchong,Song Libing,Wan Qianfen,et al. cMyc-mediated activation of serine biosynthesis pathway is critical for cancer progression under nutrient deprivation conditions[J]. Cell Research,2015,25(4):429.
APA Sun Linchong.,Song Libing.,Wan Qianfen.,Wu Gongwei.,Li Xinghua.,...&Zhang Huafeng.(2015).cMyc-mediated activation of serine biosynthesis pathway is critical for cancer progression under nutrient deprivation conditions.Cell Research,25(4),429.
MLA Sun Linchong,et al."cMyc-mediated activation of serine biosynthesis pathway is critical for cancer progression under nutrient deprivation conditions".Cell Research 25.4(2015):429.
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