Details

Autor(en) / Beteiligte

• Sun, Linchong
• Song, Libing
• Wan, Qianfen
• Wu, Gongwei
• Li, Xinghua
• Wang, Yinghui
• Wang, Jin
• Liu, Zhaoji
• Zhong, Xiuying
• He, Xiaoping
• Shen, Shengqi
• Pan, Xin
• Li, Ailing
• Wang, Yulan
• Gao, Ping
• Tang, Huiru
• Zhang, Huafeng

Titel

cMyc-mediated activation of serine biosynthesis pathway is critical for cancer progression under nutrient deprivation conditions

Ist Teil von

• Cell research, 2015-04, Vol.25 (4), p.429-444

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2015

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• Cancer 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 condi- tions. Here we show that deprivation of glucose or glutamine, two major nutrition sources for cancer cells, dramat- ically 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 cMye led to elevated glutathione （GSH） production, cell cycle progression and nucleic acid synthesis, which are essential for cell survival and proliferation especially un- der nutrient-deprived conditions. We further uncovered that phosphoserine phosphatase （PSPH）, the final rate-lim- iting enzyme of the SSP pathway, is critical for cMyc-driven cancer progression both in vitro and in vivo, and impor- tantly, 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 activa- tion, an essential part of metabolic switch, to facilitate cancer progression under nutrient-deprived conditions.