PIK3CD induces cell growth and invasion by activating AKT/GSK-3β/β-catenin signaling in colorectal cancer

Autor: Ying-Kang Xie, Rong-Chang Wang, Shi-Hao Dong, Jiong-Qiang Huang, Bing Luo, Ze-Kun Jiang, Jian-Feng Zhong, Guang-Ming Wen, Wei Yi, Jing-Song Chen
Rok vydání: 2019
Předmět:
0301 basic medicine
Cancer Research
Class I Phosphatidylinositol 3-Kinases
Colorectal cancer
colorectal cancer
03 medical and health sciences
0302 clinical medicine
Cell
Molecular
and Stem Cell Biology
Cell Movement
In vivo
Cell Line
Tumor
medicine
Humans
Neoplasm Invasiveness
RNA
Small Interfering
growth
invasion
Protein kinase B
beta Catenin
PI3K/AKT/mTOR pathway
Cell Proliferation
Glycogen Synthase Kinase 3 beta
Kinase
Cell growth
Chemistry
PIK3CD
Original Articles
General Medicine
HCT116 Cells
medicine.disease
digestive system diseases
β‐catenin signaling
Gene Expression Regulation
Neoplastic
030104 developmental biology
Oncology
Cell culture
P110δ
030220 oncology & carcinogenesis
Cancer research
Original Article
Colorectal Neoplasms
HT29 Cells
Proto-Oncogene Proteins c-akt
Signal Transduction
Zdroj: Cancer Science
ISSN: 1347-9032
Popis: The catalytic subunit p110δ 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 β-catenin and T-cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional activity and decreased glycogen synthase kinase 3β (GSK-3β) 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 β-catenin. In addition, PIK3CD expression in colon cancer tissues positively correlated with β-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-3β/β-catenin signaling, suggesting that PIK3CD might be a novel prognostic biomarker and a potential therapeutic target for CRC.
Databáze: OpenAIRE
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