A Critical Role of c-Cbl-Interacting Protein of 85 kDa in the Development and Progression of Head and Neck Squamous Cell Carcinomas through the Ras-ERK Pathway
| Autor: | Hiroaki Niiro, Takahiro Wakasaki, Tadayoshi Taniyama, Koichi Akashi, Siamak Jabbarzadeh-Tabrizi, Shizuo Komune, Muneyuki Masuda, Kumiko Noda |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Cancer Research
biology Kinase Cell growth Chemistry media_common.quotation_subject medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Head and neck squamous-cell carcinoma lcsh:RC254-282 Cell biology stomatognathic diseases biology.protein medicine Phosphorylation Epidermal growth factor receptor Signal transduction Internalization Transforming growth factor media_common |
| Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 12, Iss 10, Pp 789-796 (2010) |
| ISSN: | 1522-8002 1476-5586 |
| Popis: | Activation of the transforming growth factor (TGF) α/epidermal growth factor receptor (EGFR)-mediated signaling pathway is a common mechanism for dysregulated growth of head and neck squamous cell carcinoma (HNSCC). c-Cbl-interacting protein of 85 kDa (CIN85) is an adaptor protein that facilitates EGFR internalization. Little is known, however, about a role of CIN85 in EGFR signaling as well as its relevance to tumor development and progression of HNSCC. Here, we demonstrate that CIN85 is highly expressed in HNSCC tumor samples compared with adjacent normal tissues, and this overexpression is significantly correlated with advanced clinical stage. The experiments using CIN85-overexpressing and knockdown HNSCC cell lines showed that CIN85 promotes HNSCC growth and facilitates EGFR internalization without apparently affecting phosphorylation of EGFR. Moreover, CIN85 promoted TGF-α-induced activation of Ras and phosphorylation of downstream molecules such as c-Raf, MEK, and extracellular signal-regulated kinase, leading to expression of c-Myc that is critical for sustained proliferation of HNSCC. Taken together, these findings suggest that CIN85 not only controls EGFR internalization but also promotes the EGFR-mediated tumor development and progression, and thus, CIN85 may serve as a potential therapeutic target in a subset of HNSCC. |
| Databáze: | OpenAIRE |
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