Original Article
Copyright ©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 28, 2014; 20(48): 18260-18270
Published online Dec 28, 2014. doi: 10.3748/wjg.v20.i48.18260
PBX3 promotes migration and invasion of colorectal cancer cells via activation of MAPK/ERK signaling pathway
Hai-Bo Han, Jin Gu, Deng-Bo Ji, Zhao-Wei Li, Yuan Zhang, Wei Zhao, Li-Min Wang, Zhi-Qian Zhang
Hai-Bo Han, Yuan Zhang, Wei Zhao, Li-Min Wang, Zhi-Qian Zhang, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cell Biology, Peking University Cancer Hospital and Institute, Beijing 100142, China
Jin Gu, Deng-Bo Ji, Zhao-Wei Li, Department of Colorectal Cancer Surgery, Peking University Cancer Hospital and Institute, Beijing 100142, China
Author contributions: Han HB performed the majority of experiments and wrote the manuscript; Gu J, Ji DB and Li ZW collected the data on colorectal cancer cases and follow-up; Zhang Y, Zhao W and Wang LM provided technical support for this work; and Zhang ZQ designed the study and revised the manuscript.
Supported by Beijing Natural Science Foundation, No. 5122012; National Natural Science Foundation of China, No. 81201964 and No. 81330051
Correspondence to: Zhi-Qian Zhang, PhD, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cell Biology, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Beijing 100142, China. zlzqzhang@bjmu.edu.cn
Telephone: +86-10-88196792 Fax: +86-10-88122437
Received: March 25, 2014
Revised: May 12, 2014
Accepted: May 19, 2014
Published online: December 28, 2014
Processing time: 286 Days and 18.1 Hours
Abstract

AIM: To investigate the role of pre-B-cell leukemia homeobox (PBX)3 in migration and invasion of colorectal cancer (CRC) cells.

METHODS: We detected PBX3 expression in five cell lines and surgical specimens from 111 patients with CRC using real-time reverse transcription-polymerase chain reaction. We forced expression of PBX3 in low metastatic HT-29 and SW480 cells and knocked down expression of PBX3 in highly metastatic LOVO and HCT-8 cells. Wound healing and Boyden chamber assays were used to detect cell migration and invasion after altered expression of PBX3. Western blot was performed to detect the change of signaling molecule ERK1/2 following PBX3 overexpression.

RESULTS: High level of PBX3 expression was correlated with the invasive potential of CRC cells, and significantly associated with lymph node invasion (P = 0.02), distant metastasis (P = 0.04), advanced TNM stage (P = 0.03) and poor overall survival of patients (P < 0.05). Ectopic expression of PBX3 in low metastatic cells was shown to promote migration and invasion, while inhibited PBX3 expression in highly metastatic cells suppressed migration and invasion. Furthermore, upregulation of phosphorylated extracellular signal-regulated kinase (ERK)1/2 was found to be one of the targeted molecules responsible for PBX3-induced CRC cell migration and invasion.

CONCLUSION: PBX3 induces invasion and metastasis of CRC cells partially through activation of the MAPK/ERK signaling pathway.

Keywords: Pre-B-cell leukemia homeobox 3; Colorectal cancer; Cell migration; Cell invasion; Mitogen-activated protein kinase signaling pathway

Core tip: Pre-B-cell leukemia homeobox (PBX)3 is a poor prognostic factor for colorectal cancer by promoting cell migration and invasion. We investigated the role of PBX3 in migration and invasion of colorectal cancer cells, and found that PBX3 could induce the invasion and metastasis of colorectal cancer cells partially through activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathway.