Glucose Transporter-1 Cooperating with AKT Signaling Promote Gastric Cancer Progression
Authors Zhou D, Jiang L, Jin L, Yao Y, Wang P, Zhu X
Received 27 February 2020
Accepted for publication 7 May 2020
Published 3 June 2020 Volume 2020:12 Pages 4151—4160
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Seema Singh
Diyuan Zhou,1,* Linhua Jiang,1,* Lichen Jin,1,* Yizhou Yao,1 Peijie Wang,2 Xinguo Zhu1
1Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Institute of Mental Health, The Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xinguo Zhu
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province 215006, People’s Republic of China
Institute of Mental Health, The Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu Province 215000, People’s Republic of China
Objective: High expression of GLUT1 has been observed in numerous solid cancers, facilitating glucose consumption for supporting tumor cell survival. The altered metabolic activity is regulated by series of signaling pathways, including AKT signaling that acts as a key role in glucose metabolism and shows close correlation with the malignant transformation. In this study, we aimed to elucidate the effect of GLUT1 on gastric cancer (GC) and to explore the relation between GLUT1 and AKT signaling.
Materials and Methods: GLUT1, p-AKT, and p-S6k1 expression were investigated by immunohistochemistry and semi-quantitative analysis in 57 paired-GC samples. The relationship of GLUT1 with clinical indexes in GC tissues was investigated. The effects of GLUT1 on the prognosis of GC patients and the underlying mechanism involved were studied by subgroup analysis.
Results: In GC tissues, an obvious increase in GLUT1 expression was observed when compared with that of normal tissues (P< 0.001). Advanced clinicopathological factors (tumor size P=0.019, invasion depth P=0.002, lymph node metastasis P< 0.001, differentiation P=0.024, neural invasion P=0.003, and TNM staging P=0.001) correlated with high GLUT1 levels. GLUT1 was an independent risk factor resulting in poor prognosis (P=0.002, HR=5.132). GLUT1 increased the activation ratio of p-AKT (P< 0.01) and p-S6K1 (P< 0.001) in GC. The expression of p-S6K1 and GLUT1 was positively correlated. (P=0.001, R=0.173). The survival probability of GC patients with GLUT1(+)/p-S6K1(+) was worse when compared to that of GLUT1(+)/p-S6K1(-) or GLUT1(-)/p-S6K1(+) (P< 0.001).
Conclusion: High expression of GLUT1 facilitated GC progression, leading to poor prognosis. Overexpression of GLUT1 activated AKT-S6K1 axis, resulting in adverse outcomes of GC. GLUT1 is novel indicator of GC prognosis and GLUT1 targeted metabolic treatment that has potential therapeutic value.
Keywords: AKT, gastric cancer, GLUT1, S6K1
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