Cannabinoids Promote Progression of HPV-Positive Head and Neck Squamous Cell Carcinoma via p38 MAPK Activation
| Autor: | Huwate Yeerna, Bharat A. Panuganti, Pablo Tamayo, Akihiro Sakai, Koji Ebisumoto, Yusuke Goto, Sunny Haft, J. Silvio Gutkind, Takahito Fukusumi, Andrew B. Sharabi, Jacqueline A. Hubbard, Yuki Saito, William Kim, Shuling Ren, Sayed Sadat, Mizuo Ando, Theresa Guo, Joseph A. Califano, Chao Liu |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Small interfering RNA Cannabinoid receptor medicine.medical_treatment Mice Nude Apoptosis p38 Mitogen-Activated Protein Kinases Article Small hairpin RNA 03 medical and health sciences Mice 0302 clinical medicine stomatognathic system Cell Movement medicine otorhinolaryngologic diseases Tumor Cells Cultured Animals Humans Receptors Cannabinoid Papillomaviridae Cell Proliferation Gene knockdown Cell growth business.industry Cannabinoids Squamous Cell Carcinoma of Head and Neck Papillomavirus Infections medicine.disease Prognosis Head and neck squamous-cell carcinoma Xenograft Model Antitumor Assays stomatognathic diseases 030104 developmental biology Oncology Head and Neck Neoplasms 030220 oncology & carcinogenesis Cancer research Female Cannabinoid business |
| Zdroj: | Clin Cancer Res |
| ISSN: | 1557-3265 |
| Popis: | Purpose: Human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is associated with daily marijuana use and is also increasing in parallel with increased marijuana use in the United States. Our study is designed to define the interaction between cannabinoids and HPV-positive HNSCC. Experimental Design: The expression of cannabinoid receptors CNR1 and CNR2 was analyzed using The Cancer Genome Atlas (TCGA) HNSCC data. We used agonists, antagonists, siRNAs, or shRNA-based models to explore the roles of CNR1 and CNR2 in HPV-positive HNSCC cell lines and animal models. Cannabinoid downstream pathways involved were determined by Western blotting and analyzed in a primary HPV HNSCC cohort with single-sample gene set enrichment analysis (ssGSEA) and the OncoGenome Positioning System (Onco-GPS). Results: In TCGA cohort, the expression of CNR1 and CNR2 was elevated in HPV-positive HNSCC compared with HPV-negative HNSCC, and knockdown of CNR1/CNR2 expression inhibited proliferation in HPV-positive HNSCC cell lines. Specific CNR1 and CNR2 activation as well as nonselective cannabinoid receptor activation in cell lines and animal models promoted cell growth, migration, and inhibited apoptosis through p38 MAPK pathway activation. CNR1/CNR2 antagonists suppressed cell proliferation and migration and induced apoptosis. Using whole-genome expression analysis in a primary HPV HNSCC cohort, we identified specific p38 MAPK pathway activation signature in tumors from HPV HNSCC patients with objective measurement of concurrent cannabinoid exposure. Conclusions: Cannabinoids can promote progression of HPV-positive HNSCC through p38 MAPK pathway activation. |
| Databáze: | OpenAIRE |
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