J Cancer 2019; 10(18):4196-4207. doi:10.7150/jca.34145
Verteporfin suppresses the proliferation, epithelial-mesenchymal transition and stemness of head and neck squamous carcinoma cells via inhibiting YAP1
1. Department of Pathology, Medical School of Southeast University, Nanjing 210009, China
2. Zibo Vocational Institute, Zibo 255314, China
3. Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA19104, USA
4. Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
#: These authors contributed equally to this article.
Liu K, Du S, Gao P, Zheng J. Verteporfin suppresses the proliferation, epithelial-mesenchymal transition and stemness of head and neck squamous carcinoma cells via inhibiting YAP1. J Cancer 2019; 10(18):4196-4207. doi:10.7150/jca.34145. Available from http://www.jcancer.org/v10p4196.htm
Purpose: Yes-associated protein 1 (YAP1) is overexpressed in head and neck squamous cell carcinoma (HNSCC). However, it is unknown whether verteporfin, a YAP1 inhibitor, can inhibit HNSCC cells as well as the molecular mechanisms involved.
Methods: YAP1 expression was investigated by immunohistochemistry in human head and neck carcinoma tissues (n=70). CCK-8 assay, colony formation assay, flow cytometric analysis, wound-healing assay and Transwell migration and invasion assays were used to evaluated the effects of verteporfin on the six HNSCC cell lines (three HPV-positive and three HPV-negative). The transcription and protein expression levels of YAP1 and its associated genes were investigated by real-time PCR and Western blotting, respectively. The effects of verteporfin on HNSCC cells in vivo were assessed by a xenograft model.
Results: YAP1 expression was significantly higher in carcinoma tissues than in tumor-adjacent normal tissues (n=10). A CCK-8 assay showed that the inhibitory effects of verteporfin on HNSCC cells were markedly enhanced by light activation. Verteporfin significantly inhibited HNSCC cell proliferation, migration and invasion, induced apoptosis, and arrested the cell cycle at the S/G2 phase. Verteporfin significantly attenuated the expression of genes related to epithelial-mesenchymal transition (YAP1, Snail, CTNNB1 and EGFR) and stemness (Oct4 and YAP1) and increased E-cadherin expression in HNSCC cells. Furthermore, verteporfin significantly inhibited PD-L1 expression in HNSCC cells. However, the expression levels of HPV-16 E6 and E7 did not change with VP treatment. The anticancer effect of verteporfin on HNSCC was confirmed by the inhibition of xenograft growth in vivo.
Conclusions: Our results indicate that YAP1 overexpression is involved in HNSCC tumorigenesis and verteporfin is a potential therapeutic drug for HNSCC.
Keywords: Verteporfin, YAP1, Head & neck squamous cell carcinoma, Cell proliferation, Epithelial-mesenchymal transition, Stemness