title: Wnt-C59 arrests stemness and suppresses growth of nasopharyngeal carcinoma in mice by inhibiting the Wnt pathway in the tumor microenvironment.
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.
authors.affiliation: Department of Clinical Oncology, Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Laboratory Block, Pokfulam, Hong Kong SAR, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Clinical Oncology, Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Laboratory Block, Pokfulam, Hong Kong SAR, China.
authors.forename: Yee Peng
authors.initials: YP
authors.lastname: Phoon
authors.affiliation: Department of Clinical Oncology, Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Laboratory Block, Pokfulam, Hong Kong SAR, China.
authors.forename: Xiwan
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Clinical Oncology, Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Laboratory Block, Pokfulam, Hong Kong SAR, China.
authors.forename: Shing Yee Steffi
authors.initials: SY
authors.lastname: Chong
authors.affiliation: Department of Clinical Oncology, Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Laboratory Block, Pokfulam, Hong Kong SAR, China.
authors.forename: Joseph Chok Yan
authors.initials: JC
authors.lastname: Ip
authors.affiliation: Department of Clinical Oncology, Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Laboratory Block, Pokfulam, Hong Kong SAR, China.
authors.forename: Bonnie Wing Yan
authors.initials: BW
authors.lastname: Wong
authors.affiliation: Department of Clinical Oncology, Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Laboratory Block, Pokfulam, Hong Kong SAR, China.
authors.forename: Maria Li
authors.initials: ML
authors.lastname: Lung
mesh_terms: D000818:Animals; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016147:Genes, Tumor Suppressor / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D059016:Tumor Microenvironment; D060449:Wnt Signaling Pathway / Q000235:genetics*
keywords: Wnt pathway; Wnt-C59; cancer stem cells; nasopharyngeal carcinoma; tumor suppression