Li Ye, Shen Jia, Cheng Chien-Shan, Gao HuiFeng, Zhao Jiangang, Chen Lianyu
Department of Integrated Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032 China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China.
Cell Biosci. 2020 Aug 6;10:95. doi: 10.1186/s13578-020-00457-5. eCollection 2020.
Human pyruvate dehydrogenase phosphatase 1 (PDP1) plays an important physiological role in energy metabolism; however, its expression and function in human pancreatic adenocarcinoma (PDAC) remain unknown. This study aimed to investigate the expression pattern and mechanisms of action of PDP1 in human PDAC.
The expression pattern of PDP1 in PDAC was determined, and its correlation with patient survival was analyzed. Ectopic expression or knockdown of PDP1 was performed, and in vitro proliferation and migration, as well as in vivo tumor growth of PDAC, were measured. The mechanism was studied by biochemical approaches.
PDP1 was overexpressed in human PDAC samples, and high expression of PDP1 correlated with poor overall and disease-free survival of PDAC patients. PDP1 promoted the proliferation, colony formation, and invasion of PDAC cells in vitro and facilitated orthotopic tumor growth in vivo. PDP1 accelerated intracellular ATP production, leading to sufficient energy to support rapid cancer progression. mTOR activation was responsible for the PDP1-induced tumor cell proliferation and invasion in PDAC. AMPK was downregulated by PDP1 overexpression, resulting in mTOR activation and cancer progression.
Our findings suggested that PDP1 could be a promising diagnostic and therapeutic target for anti-PDAC treatment.
人丙酮酸脱氢酶磷酸酶1（PDP1）在能量代谢中发挥重要生理作用；然而，其在人胰腺腺癌（PDAC）中的表达及功能尚不清楚。本研究旨在探讨PDP1在人PDAC中的表达模式及作用机制。
测定PDP1在PDAC中的表达模式，并分析其与患者生存的相关性。进行PDP1的异位表达或敲低，检测PDAC的体外增殖、迁移以及体内肿瘤生长情况。通过生化方法研究其机制。
PDP1在人PDAC样本中高表达，PDP1的高表达与PDAC患者较差的总生存和无病生存相关。PDP1促进PDAC细胞的体外增殖、集落形成和侵袭，并促进体内原位肿瘤生长。PDP1加速细胞内ATP生成，从而产生足够能量以支持癌症快速进展。mTOR激活介导PDP1诱导的PDAC肿瘤细胞增殖和侵袭。PDP1过表达使AMPK下调，导致mTOR激活及癌症进展。
我们的研究结果表明，PDP1可能是抗PDAC治疗的一个有前景的诊断和治疗靶点。
Zotero 插件
