WNT5A promotes stemness characteristics in nasopharyngeal carcinoma cells leading to metastasis and tumorigenesis
| Autor: | Chang Fu Yang, Xiao Qing Pei, Yan Qun Xiang, Fang Jing Zheng, Ying Ying Liang, Duan Fang Liao, An Hua Li, Yi Xin Zeng, Rui Sun, Yan Tao Yin, Ru Hai Zou, Chao Nan Qian, Bart O. Williams, Tie Bang Kang, Bi Jun Huang, Xinjian Li, Ying Na Bao, Li Qin, Li Xia Peng |
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| Rok vydání: | 2015 |
| Předmět: |
Pathology
medicine.medical_specialty Carcinogenesis Nasopharyngeal neoplasm Mice Nude Biology Transfection medicine.disease_cause Wnt-5a Protein Metastasis Mice Side population Cancer stem cell Cell Line Tumor Proto-Oncogene Proteins otorhinolaryngologic diseases medicine metastasis Animals Humans PKC Neoplasm Metastasis Mice Inbred BALB C Nasopharyngeal Carcinoma Carcinoma Wnt signaling pathway Nasopharyngeal Neoplasms medicine.disease Recombinant Proteins Wnt Proteins body regions tumorigenesis stomatognathic diseases Oncology Nasopharyngeal carcinoma embryonic structures Cancer research Heterografts Female sense organs Stem cell WNT5A Research Paper |
| Zdroj: | ResearcherID Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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