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Protein kinase C-iota-mediated glycolysis promotes non-small-cell lung cancer progression

Authors Liu L, Lei B, Wang L, Chang C, Yang H, Liu J, Huang G, Xie W

Received 1 March 2019

Accepted for publication 18 June 2019

Published 18 July 2019 Volume 2019:12 Pages 5835—5848

DOI https://doi.org/10.2147/OTT.S207211

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Ms Aruna Narula

Peer reviewer comments 2

Editor who approved publication: Dr Gaetano Romano


Liu Liu1,*, Bei Lei1,*, Lihua Wang,1 Cheng Chang,1 Hao Yang,2 Jianjun Liu,3 Gang Huang,1–3 Wenhui Xie1

1Department of Nuclear Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory for Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, People’s Republic of China; 3Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Purpose: To determine whether protein kinase C-iota (PKC-iota) is associated with glucose metabolism in non-small-cell lung cancer (NSCLC) and whether its regulatory effect on metabolic and biological changes observed in NSCLC can be mediated by glucose transporter 1 (GLUT1).
Patients and methods: Forty-five NSCLC patients underwent combined 18F-fludeoxyglucose (18F-FDG) positron emission tomography and computed tomography (PET/CT) before surgery, and another eighty-one NSCLC patients were followed-up for 1–91 months after tumor resection. The rate of glucose metabolism in NSCLC was quantified by measuring the maximum standardized uptake value (SUVmax) by 18F-FDG PET/CT. PKC-iota and GLUT1 in NSCLC were detected by immunostaining. In vitro, PKC-iota was knocked down, whereas GLUT1 was silenced with or without PKC-iota overexpression to identify the role of PKC-iota in glycolysis. Spearman’s rank correlation coefficient was used in the correlation analysis. Kaplan-Meier analysis was used to assess survival duration.
Results: There was a positive relationship between PKC-iota expression and SUVmax in NSCLC (r=0.649, P<0.001). PKC-iota expression also showed a positive relationship with GLUT1 in NSCLC tissues (r=0.686, P<0.001). Patients whose NSCLC tissues highly co-expressed PKC-iota and GLUT1 had worse prognosis compared with patients without high co-expression of PKC-iota and GLUT1. In vitro, PKC-iota silencing significantly decreased the expression of GLUT1 and inhibited glucose uptake and glycolysis; c-Myc silencing restrained PKC-iota-mediated GLUT1 elevation; GLUT1 knockdown remarkably suppressed PKC-iota-mediated glycolysis and cell growth.
Conclusion: In NSCLC, the rate of glucose metabolism was positively correlated with PKC-iota expression. PKC-iota increased glucose accumulation and glycolysis by upregulating c-Myc/GLUT1 signaling and is thus involved in tumor progression.

Keywords: protein kinase C-iota, glucose transporter 1, 18F-fludeoxyglucose, glycolysis, non-small-cell lung cancer

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