Hormad1 Plays An Important Role In The Hnscc Carcinogenesis

Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer worldwide. Approximately one-third of patients present with early-stage disease and these patients are treated with either surgery or radiotherapy, with cure rates of 70-90%. The majority of patients, however, present with locally advanced stage disease. Radical treatment in this situation requires multimodality therapy with surgery, commonly followed by postoperative radiotherapy or chemotherapy. These treatments are intensive and associated with severe acute toxicity and long-term sequelae. Despite recent advances in both surgical and radiotherapy delivery techniques, up to 50% of locally advanced tumours relapse usually within the first 2 years after treatment. The development of novel therapeutic approaches and their integration into the current forms of treatment is of great interest to improve the therapeutic efficacy. Immunotherapy may provide an alternative for current treatment approach. Cancer/testis antigens (CTAs) are a family of tumor-associated antigens expressed in human tumors of different histological origin, but not in normal tissues except for testis and placenta. This tumor-restricted pattern of expression, together with their strong in vivo immunogenicity, identified CTA as ideal targets for tumor-specific immunotherapeutic approaches. A screening for CTAs expressed in HNSCC detected HORMAD1 recurrently expressed in these tumors. Objectives: The aim of this study is better understand the role of HORMAD1 in HNSCC by evaluating its influence in different tumorigenic processes, such as apoptosis, cell cycle and migration. Methods: The HORMAD1 expression was evaluated in HNSCC cell lines by RT-PCR and the presence of HORMAD1 protein was confirmed by Western Blot. HORMAD1 expression was silenced by shRNA and assays were conducted to evaluate the impact of HORMAD1 absence in cell cycle regulation and apoptosis. Results: The HORMAD1 gene was knocked-down in a HNSCC cell line and functional assays revealed a reduction in the proportion of the cells in the G1 phase of cell cycle and an induction of the apoptosis when HORMAD1 is absent. Conclusions: Our results demonstrate that HORMAD1 is frequently expressed in HNSCC and our in vitro observations indicate that this CTA may play an important role in the HNSCC carcinogenesis. Citation Format: Viviane Carlin, Dorival Mendes Rodrigues-Junior, Thais Priscila Biassi, Bruno Heidi Nakano Nozima, Marcus Vinicius Buri, Andre Luiz Vettore. HORMAD1 plays an important role in the HNSCC carcinogenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3953. doi:10.1158/1538-7445.AM2015-3953