Snail reprograms glucose metabolism by repressing phosphofructokinase PFKP allowing cancer cell survival under metabolic stress

被引：173

作者：

Kim, Nam Hee ^{[1
]}

Cha, Yong Hoon ^{[1
,9
]}

Lee, Jueun ^{[2
,3
]}

Lee, Seon-Hyeong ^{[4
]}

Yang, Ji Hye ^{[1
]}

Yun, Jun Seop ^{[1
]}

Cho, Eunae Sandra ^{[1
]}

Zhang, Xianglan ^{[1
,5
]}

Nam, Miso ^{[2
,3
]}

Kim, Nami ^{[2
]}

Yuk, Young-Su ^{[1
]}

Cha, So Young ^{[1
]}

Lee, Yoonmi ^{[1
]}

Ryu, Joo Kyung ^{[1
]}

Park, Sunghyouk ^{[6
]}

Cheong, Jae-Ho ^{[7
]}

Kang, Sang Won ^{[8
]}

Kim, Soo-Youl ^{[4
]}

Hwang, Geum-Sook ^{[2
]}

Yook, Jong In ^{[1
]}

Kim, Hyun Sil ^{[1
]}

机构：

[1] Yonsei Univ, Coll Dent, Oral Canc Res Inst, Dept Oral Pathol, Seoul 03722, South Korea

[2] Korea Basic Sci Inst, Western Seoul Ctr, Integrated Metabol Res Grp, Seoul 03760, South Korea

[3] Sungkyunkwan Univ, Dept Chem, Suwon 16419, South Korea

[4] Natl Canc Ctr, Canc Cell & Mol Biol Branch, Ilsan 10408, South Korea

[5] Yanbian Univ, Coll Med, Dept Pathol, Yanji 133000, Jilin Province, Peoples R China

[6] Seoul Natl Univ, Coll Pharm, Nat Prod Res Inst, Seoul 08826, South Korea

[7] Yonsei Univ, Coll Med, Dept Surg, Seoul 03722, South Korea

[8] Ewha Womans Univ, Res Ctr Cell Homeostasis, Dept Life Sci, Seoul 03760, South Korea

[9] Yonsei Univ, Coll Dent, Dept Oral & Maxillofacial Surg, Seoul 120752, South Korea

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

新加坡国家研究基金会;

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; PENTOSE-PHOSPHATE PATHWAY; BREAST-CANCER; PYRUVATE-KINASE; DUAL REGULATION; TUMOR-GROWTH; STEM-CELLS; TRANSCRIPTION; ANTIOXIDANT; METASTASIS;

D O I：

10.1038/ncomms14374

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Dynamic regulation of glucose flux between aerobic glycolysis and the pentose phosphate pathway (PPP) during epithelial-mesenchymal transition (EMT) is not well-understood. Here we show that Snail (SNAI1), a key transcriptional repressor of EMT, regulates glucose flux toward PPP, allowing cancer cell survival under metabolic stress. Mechanistically, Snail regulates glycolytic activity via repression of phosphofructokinase, platelet (PFKP), a major isoform of cancer-specific phosphofructokinase-1 (PFK-1), an enzyme involving the first rate-limiting step of glycolysis. The suppression of PFKP switches the glucose flux towards PPP, generating NADPH with increased metabolites of oxidative PPP. Functionally, dynamic regulation of PFKP significantly potentiates cancer cell survival under metabolic stress and increases metastatic capacities in vivo. Further, knockdown of PFKP rescues metabolic reprogramming and cell death induced by loss of Snail. Thus, the Snail-PFKP axis plays an important role in cancer cell survival via regulation of glucose flux between glycolysis and PPP.

引用

页数：12

共 56 条

[1] Models, mechanisms and clinical evidence for cancer dormancy [J].