Oncotarget

Research Papers:

AEG-1 activates Wnt/PCP signaling to promote metastasis in tongue squamous cell carcinoma

Yunping Pan, Xu Guo, Zheng Yang, Shan Chen, Yiyan Lei, Millicent Lin, Liantang Wang, Chongjin Feng and Zunfu Ke _

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Oncotarget. 2016; 7:2093-2104. https://doi.org/10.18632/oncotarget.6573

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Abstract

Yunping Pan1,2,*, Xu Guo3,*, Zheng Yang2,*, Shan Chen1, Yiyan Lei4, Millicent Lin5, Liantang Wang2, Chongjin Feng1, Zunfu Ke2

1Department of Stomatology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Province Guangdong, P.R.China

2Department of Pathology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Province Guangdong, P.R.China

3Department of Gynecology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Province Guangdong, P.R. China

4Department of Chest Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Province Guangdong, P.R.China

5Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging (CIMI), California NanoSystems Institute (CNSI), University of California, Los Angeles, California, USA

*These authors have contributed equally to this work

Correspondence to:

Zunfu Ke, e-mail: [email protected]

Chongjin Feng, e-mail: [email protected]

Keywords: AEG-1, epithelial-mesenchymal transition, tongue squamous cell carcinoma, Wnt/PCP, metastasis

Received: August 07, 2015     Accepted: November 25, 2015     Published: December 12, 2015

ABSTRACT

Despite advances in therapy, survival among patients with locally advanced squamous cell carcinoma of tongue (TSCC) and cervical lymph node metastasis remains dismal. Here, we estimated the functional effect of AEG-1 on TSCC metastasis and explored the molecular mechanism by which AEG-1 stimulates epithelial-mesenchymal transition (EMT). We initially found that AEG-1 mRNA levels were much higher in metastatic TSCC than in non-metastatic TSCC and that AEG-1 expression strongly correlates with EMT status. Receiver operating characteristic analysis showed that the combined AEG-1 and EMT statuses are predictive of the survival rate among TSCC patients. In addition, AEG-1 knockdown inhibited EMT in cultured TSCC cell lines and in a xenograft-mouse model. Recombinant AEG-1 activated Wnt/PCP-Rho signaling, and its stimulatory effects on TSCC cell invasiveness and EMT were reversed by an anti-Wnt5a neutralizing antibody or by inhibition of Rac1 or ROCK. These results highlight the critical stimulatory effect of AEG-1 on cancer cell invasiveness and EMT and indicate that AEG-1 may be a useful prognostic biomarker for TSCC patients.


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