Oncotarget

Research Papers:

Wnt-C59 arrests stemness and suppresses growth of nasopharyngeal carcinoma in mice by inhibiting the Wnt pathway in the tumor microenvironment

Yue Cheng, Yee Peng Phoon, Xiwan Jin, Shing Yee Steffi Chong, Joseph Chok Yan Ip, Bonnie Wing Yan Wong and Maria Li Lung _

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Oncotarget. 2015; 6:14428-14439. https://doi.org/10.18632/oncotarget.3982

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Abstract

Yue Cheng1, Yee Peng Phoon1, Xiwan Jin1, Shing Yee Steffi Chong1, Joseph Chok Yan Ip1, Bonnie Wing Yan Wong1 and Maria Li Lung1

1 Department of Clinical Oncology, Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Laboratory Block, Pokfulam, Hong Kong SAR, China

Correspondence to:

Yue Cheng, email:

Maria Li Lung, email:

Keywords: Wnt-C59, nasopharyngeal carcinoma, cancer stem cells, Wnt pathway, tumor suppression

Received: December 15, 2014 Accepted: April 10, 2015 Published: May 04, 2015

Abstract

Wnt/β-catenin signaling is responsible for the generation of cancer stem cells (CSCs) in many human tumors, including nasopharyngeal carcinoma (NPC). Recent studies demonstrate that Wnt or PORCN inhibitor, Wnt-C59, inhibits tumor growth in MMTV-WNT1 transgenic mice. The effect of Wnt-C59 in human tumors is not clear. In this study, the NPC cell lines investigated manifest heterogeneous responses to Wnt-C59 treatment. Wnt-C59 decreased tumor growth of SUNE1 cells in mice immediately following the administration of Wnt-C59. Mice injected with HNE1 cells did not develop visible tumors after the treatment of Wnt-C59, while control mice developed 100% tumors. Wnt-C59 inhibited stemness properties of NPC cells in a dosage-dependent manner by arresting sphere formation in both HNE1 and SUNE1 cells. Thus, Wnt-C59 has the potential to eradicate CSCs in human tumors. Active β-catenin and Axin2 proteins were strongly expressed in stromal cells surrounding growing tumors, confirming the importance of Wnt signaling activities in the microenvironment being driving forces for cell growth. These novel findings confirm the ability of Wnt-C59 to suppress Wnt-driven undifferentiated cell growth in NPC. Both anti-Wnt signaling and anti-CSC approaches are feasible strategies in cancer therapy.


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