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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2017

Open Access 01-12-2017 | Research

CDC42-interacting protein 4 promotes metastasis of nasopharyngeal carcinoma by mediating invadopodia formation and activating EGFR signaling

Authors: Dong-Fang Meng, Ping Xie, Li-Xia Peng, Rui Sun, Dong-Hua Luo, Qiu-Yan Chen, Xing Lv, Lin Wang, Ming-Yuan Chen, Hai-Qiang Mai, Ling Guo, Xiang Guo, Li-Sheng Zheng, Li Cao, Jun-Ping Yang, Meng-Yao Wang, Yan Mei, Yuan-Yuan Qiang, Zi-Meng Zhang, Jing-Ping Yun, Bi-Jun Huang, Chao-Nan Qian

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2017

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Abstract

Background

Nasopharyngeal carcinoma (NPC) is a common malignancy in Southern China and Southeast Asia. In this study, we investigated the functional and molecular mechanisms by which CDC42-interacting protein 4 (CIP4) influences NPC.

Methods

The expression levels of CIP4 were examined by Western blot, qRT-PCR or IHC. MTT assay was used to detect the proliferative rate of NPC cells. The invasive abilities were examined by matrigel and transwell assay. The metastatic abilities of NPC cells were revealed in BALB/c nude mice.

Results

We report that CIP4 is required for NPC cell motility and invasion. CIP4 promotes the activation of N-WASP that controls invadopodia formation and activates EGFR signaling, which induces downstream MMP2 (matrix metalloproteinase 2) upregulation. In addition, CIP4 could promote NPC metastasis by activating the EGFR pathway. In nude mouse models, distant metastasis was significantly inhibited in CIP4-silenced groups. High CIP4 expression is an independent adverse prognostic factor of overall survival (OS) and distant metastasis-free survival (DMFS).

Conclusion

We identify the critical role of CIP4 in metastasis of NPC which suggest that CIP4 may be a potential therapeutic target of NPC patients.
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Metadata
Title
CDC42-interacting protein 4 promotes metastasis of nasopharyngeal carcinoma by mediating invadopodia formation and activating EGFR signaling
Authors
Dong-Fang Meng
Ping Xie
Li-Xia Peng
Rui Sun
Dong-Hua Luo
Qiu-Yan Chen
Xing Lv
Lin Wang
Ming-Yuan Chen
Hai-Qiang Mai
Ling Guo
Xiang Guo
Li-Sheng Zheng
Li Cao
Jun-Ping Yang
Meng-Yao Wang
Yan Mei
Yuan-Yuan Qiang
Zi-Meng Zhang
Jing-Ping Yun
Bi-Jun Huang
Chao-Nan Qian
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2017
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-016-0483-z

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