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SLC5A1 promotes growth and proliferation of pancreatic carcinoma via glucose-dependent AMPK/mTOR signaling

Authors Gao HF, Chen LY, Cheng CS, Chen H, Meng ZQ, Chen Z

Received 21 November 2018

Accepted for publication 11 February 2019

Published 12 April 2019 Volume 2019:11 Pages 3171—3185


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Beicheng Sun

Hui-Feng Gao,1,2,* Lian-Yu Chen,1,2,* Chien-Shan Cheng,1,2 Hao Chen,1,2 Zhi-Qiang Meng,1,2 Zhen Chen1,2

1Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China; 2Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China

*These authors contributed equally to this work

Background: Accumulating studies have reported that aberrant expression of SLC5A1 is a negative prognostic factor to various cancer patients.
Purpose: Pancreatic cancer tissue has also shown to harbor higher expression of SLC5A1, however how SLC5A1 mediates pancreatic cancer cells growth remains unclear.
Methods: In this study, we examined the mRNA and protein expressions of SLC5A1 in human pancreatic tissue and various cell lines. The in vitro and in vivo roles of SLC5A1 in pancreatic cancer were investigated through stably transfected pancreatic cells with shRNA plasmid targeting SLC5A1.
Results: Our results observed SLC5A1 was over-expressed in human pancreatic cancer tissues as well as most pancreatic cancer cell lines. Both in vitro and in vivo inhibition of SLC5A1 retarded pancreatic cancer cell growth and progression. The SLC5A1 knockdown mediated growth suppression is mainly regulated by reduced cellular glucose uptake by pancreatic cancer cells. Our further mechanistic observation showed that inhibition of SLC5A1 induced AMPK-dependent mTOR suppression and pharmacological inhibition of AMPK rescued the effect of SLC5A1 blockade. Further protein-protein interaction analysis showed association of SLC5A1 with EGFR and knockdown of EGFR also showed decreased cellular survival and glucose uptake by pancreatic cancer cells.
Conclusion: Our findings postulated SLC5A1/EGFR as the potential therapeutic target of pancreatic cancer patients.

Keywords: pancreatic cancer, SLC5A1, EGFR, cancer cell survival

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