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Lamc1 promotes the Warburg effect in hepatocellular carcinoma cells by regulating PKM2 expression through AKT pathway

delete2019-02-12
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OA
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G
GuanXiong Ye
Y
Yong Qin *
S
Shi Wang
D
Debiao Pan
S
Shengqian Xu
吴成君 (Chengjun Wu)
X
Xinmei Wang
王俊 (Jun Wang)
H
Hai‐Lin Ye
H
He‐Juan Shen
DOI:10.1080/15384047.2018.1564558delete
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Abstract

Abstract

En 中文
Hepatocellular carcinoma (HCC), the most common aggressive malignancy of liver, is the third leading cause of cancer death across the world. Laminin gamma 1 (Lamc1), encodes laminin-gamma 1, an extracellular matrix protein involved in various progresses such as tumor cell proliferation and metabolism. In the present study, high expression of Lamc1 and PKM2 was observed in tumor tissues of HCC patients. In vitro, down-regulation of Lamc1 inhibited proliferation of HCC cells by promoting cell death, reduced glucose consumption and lactate production, accompanied by a decrease in the expression of glucose transporter 1 (GLUT1) and lactate dehydrogenase A (LDHA), and PTEN increased, as well as PTEN S380 and AKT S473/T308 phosphorylation decreased, while Lamc1 up-regulation had the opposite effect. The effects of PKM2 were similar to that of Lamc1 and markedly counteracted the effects of Lamc1 down-regulation. In addition, Lamc1-induced increase in PKM2 expression was strongly attenuated by a PI3K inhibitor, LY294002 or a si-p110 PI3K, with a significant decrease in GLUT1 and LDHA expression, as well as decreased AKT T308 phosphorylation. Thus, we speculated that Lamc1 was implicated in the progression of HCC probably by regulating PKM2 expression through PTEN/AKT pathway.
Keywords:
Lamc1
hepatocellular carcinoma
PKM2
PTEN
AKT pathway
LY294002
si-p110 PI3K
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Cancer Biology and Therapy
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Lishui University
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