期刊
CANCER SCIENCE
卷 110, 期 3, 页码 997-1011出版社
WILEY
DOI: 10.1111/cas.13931
关键词
beta-catenin signaling; colorectal cancer; growth, invasion; PIK3CD
类别
资金
- National Natural Science Foundation of China [81572424]
- Guangzhou Municipal Science and Technology Project [201607010164]
- Natural Science Foundation of Guangdong Province [2017A030313482]
- Scientific Research Project of Guangzhou Municipal Colleges and Universities [1201610322]
The catalytic subunit p110 delta of phosphoinositide 3-kinase (PI3K) encoded by PIK3CD has been implicated in some human solid tumors. However, its roles in colorectal cancer (CRC) remain largely unknown. Here we found that PIK3CD was overexpressed in colon cancer tissues and CRC cell lines and was an independent predictor for overall survival (OS) of patients with colon cancer. The ectopic overexpression of PIK3CD significantly promoted CRC cell growth, migration and invasion in vitro and tumor growth in vivo. In contrast, inhibition of PIK3CD by specific small-interfering RNA or idelalisib dramatically suppressed CRC cell growth, migration and invasion in vitro and tumor growth in vivo. Moreover, PIK3CD overexpression increased AKT activity, nuclear translocation of beta-catenin and T-cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional activity and decreased glycogen synthase kinase 3 beta (GSK-3 beta) activity, whereas PIK3CD inhibition exhibited the opposite effects. Furthermore, PIK3CD-mediated cell growth, migration and invasion were reversed by blockade of AKT signaling or depletion of beta-catenin. In addition, PIK3CD expression in colon cancer tissues positively correlated with beta-catenin abnormal expression, which was an independent predictor for OS of colon cancer patients. Taken together, our findings demonstrate that PIK3CD is an independent prognostic factor in CRC and that PIK3CD induces CRC cell growth, migration and invasion by activating AKT/GSK-3 beta/beta-catenin signaling, suggesting that PIK3CD might be a novel prognostic biomarker and a potential therapeutic target for CRC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据