已入深夜,您辛苦了!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!祝你早点完成任务,早点休息,好梦!

CD147 promotes reprogramming of glucose metabolism and cell proliferation in HCC cells by inhibiting the p53-dependent signaling pathway

瓦博格效应 厌氧糖酵解 癌细胞 细胞生物学 新陈代谢 信号转导 糖酵解 化学 PI3K/AKT/mTOR通路 癌症研究 过剩1 葡萄糖摄取 蛋白激酶B 细胞生长 下调和上调 生物 癌症 生物化学 内分泌学 遗传学 胰岛素 基因
作者
Qichao Huang,Jibin Li,Jinliang Xing,Weiwei Li,Hongwei Li,Xia Ke,Jing Zhang,Tingting Ren,Yukui Shang,Hushan Yang,Jian‐Li Jiang,Zhi‐Nan Chen
出处
期刊:Journal of Hepatology [Elsevier]
卷期号:61 (4): 859-866 被引量:137
标识
DOI:10.1016/j.jhep.2014.04.035
摘要

Background & Aims Cancer cells exhibit the reprogrammed metabolism characterized by high level of glycolysis even in the presence of oxygen. Aerobic glycolysis, known as the Warburg effect, supplies cancer cells with the substrates required for biomass generation. To date, several intracellular signaling mediators have been identified in metabolic regulation of cancer cells. However, it remains largely ambiguous how molecules on the cell surface are involved in regulation of cancer metabolism. Methods In the current study, we established several HCC cell lines differing in their CD147 (a typical transmembrane glycoprotein) expression status by zinc-finger nuclease and RNAi techniques. Then, we systematically investigated the role of CD147 in the regulation of the Warburg effect in HCC cells and explored the underlying mechanism. Results We found that CD147 significantly contributed to the reprogramming of glucose metabolism in HCC cells through a p53-dependent way. CD147 facilitated the cell surface expression of MCT1 and lactate export, which led to activation of the PI3K/Akt/MDM2 pathway and thus increased p53 degradation. The gain/loss-of-function studies demonstrated that while CD147 promoted glycolysis, mediated by p53-dependent upregulation of GLUT1 and activation of PFKL, it inhibited mitochondrial biogenesis and functions, mediated by p53-dependent downregulation of PGC1α, TFAM, and p53R2. Additionally, proliferation of HCC cells was suppressed by blocking CD147 and/or MCT1, which resulted in down-regulation of glucose metabolism. Conclusions We demonstrate that CD147 is a crucial regulator of glucose metabolism. Cancer cells exhibit the reprogrammed metabolism characterized by high level of glycolysis even in the presence of oxygen. Aerobic glycolysis, known as the Warburg effect, supplies cancer cells with the substrates required for biomass generation. To date, several intracellular signaling mediators have been identified in metabolic regulation of cancer cells. However, it remains largely ambiguous how molecules on the cell surface are involved in regulation of cancer metabolism. In the current study, we established several HCC cell lines differing in their CD147 (a typical transmembrane glycoprotein) expression status by zinc-finger nuclease and RNAi techniques. Then, we systematically investigated the role of CD147 in the regulation of the Warburg effect in HCC cells and explored the underlying mechanism. We found that CD147 significantly contributed to the reprogramming of glucose metabolism in HCC cells through a p53-dependent way. CD147 facilitated the cell surface expression of MCT1 and lactate export, which led to activation of the PI3K/Akt/MDM2 pathway and thus increased p53 degradation. The gain/loss-of-function studies demonstrated that while CD147 promoted glycolysis, mediated by p53-dependent upregulation of GLUT1 and activation of PFKL, it inhibited mitochondrial biogenesis and functions, mediated by p53-dependent downregulation of PGC1α, TFAM, and p53R2. Additionally, proliferation of HCC cells was suppressed by blocking CD147 and/or MCT1, which resulted in down-regulation of glucose metabolism. We demonstrate that CD147 is a crucial regulator of glucose metabolism.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
摇摇奶昔完成签到,获得积分20
1秒前
2秒前
刘四毛完成签到,获得积分10
2秒前
2秒前
2秒前
百浪多息发布了新的文献求助10
3秒前
3秒前
5秒前
刘四毛发布了新的文献求助10
6秒前
摇摇奶昔发布了新的文献求助10
6秒前
我是老大应助QSY采纳,获得10
6秒前
huangshoukun发布了新的文献求助10
7秒前
上官若男应助beckywyn采纳,获得10
7秒前
7秒前
11秒前
科研通AI2S应助食欲百里采纳,获得10
12秒前
顾矜应助百浪多息采纳,获得10
13秒前
13秒前
从容芮给猴王的求助进行了留言
15秒前
15秒前
科研小南完成签到,获得积分10
17秒前
朝露发布了新的文献求助10
19秒前
hihihi关注了科研通微信公众号
20秒前
亮liang发布了新的文献求助10
20秒前
汉堡包应助rr采纳,获得10
21秒前
21秒前
英俊的铭应助Tokgo采纳,获得10
22秒前
大个应助标701010采纳,获得30
22秒前
深情安青应助huangshoukun采纳,获得10
23秒前
23秒前
jinjinjin完成签到 ,获得积分10
24秒前
24秒前
24秒前
zzzsss发布了新的文献求助10
25秒前
26秒前
26秒前
Orange应助桃桃采纳,获得10
28秒前
babe发布了新的文献求助10
29秒前
QSY发布了新的文献求助10
29秒前
wangchu完成签到 ,获得积分10
29秒前
高分求助中
The late Devonian Standard Conodont Zonation 2000
Nickel superalloy market size, share, growth, trends, and forecast 2023-2030 2000
The Lali Section: An Excellent Reference Section for Upper - Devonian in South China 1500
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger 800
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 800
Saponins and sapogenins. IX. Saponins and sapogenins of Luffa aegyptica mill seeds (black variety) 500
Fundamentals of Dispersed Multiphase Flows 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3261305
求助须知:如何正确求助?哪些是违规求助? 2902122
关于积分的说明 8318843
捐赠科研通 2571905
什么是DOI,文献DOI怎么找? 1397353
科研通“疑难数据库(出版商)”最低求助积分说明 653708
邀请新用户注册赠送积分活动 632216