当前位置: X-MOL 学术Br. J. Cancer › 论文详情
Protein kinase D1 regulates metabolic switch in pancreatic cancer via modulation of mTORC1.
British Journal of Cancer ( IF 5.791 ) Pub Date : 2019-12-10 , DOI: 10.1038/s41416-019-0629-9
Sonam Kumari,Sheema Khan,Radhika Sekhri,Hassan Mandil,Stephen Behrman,Murali M Yallapu,Subhash C Chauhan,Meena Jaggi

BACKGROUND Protein kinase D1 (PKD1) is a serine-threonine kinase that regulates various functions within the cell. Herein, we report the significance of PKD1 expression in glucose metabolism resulting in pancreatic cancer (PanCa) progression and chemo-resistance. METHODS PKD1 expression in PanCa was investigated by using immunohistochemistry. Functional and metabolic assays were utilised to analyse the effect of PKD1 expression/knockdown on associated cellular/molecular changes. RESULTS PKD1 expression was detected in human pancreatic intraepithelial neoplasia lesions (MCS = 12.9; P < 0.0001) and pancreatic ductal adenocarcinoma samples (MCS = 15, P < 0.0001) as compared with faint or no expression in normal pancreatic tissues (MCS = 1.54; P < 0.0001). Our results determine that PKD1 enhances glucose metabolism in PanCa cells, by triggering enhanced tumorigenesis and chemo-resistance. We demonstrate that mTORC1 activation by PKD1 regulates metabolic alterations in PanCa cells. siRNA knockdown of Raptor or treatment with rapamycin inhibited PKD1-accelerated lactate production as well as glucose consumption in cells, which confirms the association of mTORC1 with PKD1-induced metabolic alterations. CONCLUSION This study suggests a novel role of PKD1 as a key modulator of the glucose metabolism in PanCa cells accelerating tumorigenesis and chemo-resistance. The remodelling of PKD1-dysregulated glucose metabolism can be achieved by regulation of mTORC1 for development of novel therapeutic strategies.
更新日期:2019-12-11

 

全部期刊列表>>
物理学研究前沿热点精选期刊推荐
chemistry
《自然》编辑与您分享如何成为优质审稿人-信息流
欢迎报名注册2020量子在线大会
化学领域亟待解决的问题
材料学研究精选新
GIANT
自然职场线上招聘会
科研绘图
ACS ES&T Engineering
ACS ES&T Water
屿渡论文,编辑服务
阿拉丁试剂right
张晓晨
田蕾蕾
李闯创
刘天飞
隐藏1h前已浏览文章
课题组网站
新版X-MOL期刊搜索和高级搜索功能介绍
ACS材料视界
天合科研
x-mol收录
X-MOL
苏州大学
廖矿标
深圳湾
试剂库存
down
wechat
bug