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Oncotarget. 2015 Apr 30;6(12):10239-52.

WNT5A promotes stemness characteristics in nasopharyngeal carcinoma cells leading to metastasis and tumorigenesis.

Author information

1
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
2
Hunan Province Engineering Research Center of Bioactive Substance Discovery of Traditional Chinese Medicine, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, China.
3
Division of Pharmacoproteomics, Institute of Pharmacy and Pharmacology, University of South China, Hengyang, Hunan, China.
4
Department of Radiotherapy, Ningde Municipal Hospital, Fujian Medical University Affiliated Hospital, Ningde, Fujian, China.
5
Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
6
Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
7
Department of Ultrasonography, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
8
Division of Stem Cell Regulation and Application, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, China.
9
Laboratory of Cell Signaling and Carcinogenesis, Van Andel Research Institute, Grand Rapids, Michigan, USA.

Abstract

Nasopharyngeal carcinoma (NPC) has the highest metastasis rate among head and neck cancers with unclear mechanism. WNT5A belongs to the WNT family of cysteine-rich secreted glycoproteins. Our previous high-throughput gene expression profiling revealed that WNT5A was up-regulated in highly metastatic cells. In the present study, we first confirmed the elevated expression of WNT5A in metastatic NPC tissues at both the mRNA and protein levels. We then found that WNT5A promoted epithelial-mesenchymal transition (EMT) in NPC cells, induced the accumulation of CD24-CD44+ cells and side population, which are believed to be cancer stem cell characteristics. Moreover, WNT5A promoted the migration and invasion of NPC cells in vitro, while in vivo treatment with recombinant WNT5A promoted lung metastasis. Knocking down WNT5A diminished NPC tumorigenesis in vivo. When elevated expression of WNT5A coincided with the elevated expression of vimentin in the primary NPC, the patients had a poorer prognosis. Among major signaling pathways, protein kinase C (PKC) signaling was activated by WNT5A in NPC cells. A positive feedback loop between WNT5A and phospho-PKC to promote EMT was also revealed. Taken together, these data suggest that WNT5A is an important molecule in promoting stem cell characteristics in NPC, leading to tumorigenesis and metastasis.

KEYWORDS:

PKC; WNT5A; metastasis; nasopharyngeal carcinoma; tumorigenesis

PMID:
25823923
PMCID:
PMC4496352
DOI:
10.18632/oncotarget.3518
[Indexed for MEDLINE]
Free PMC Article

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