Transcription Factors and Markers Related to Epithelial-Mesenchymal Transition and Their Role in Resistance to Therapies in Head and Neck Cancers.

Abstract

Head and neck cancers (HNCs) are heterogeneous and aggressive tumors of the upper aerodigestive tract. Although various histological types exist, the most common is squamous cell carcinoma (HNSCC). The incidence of HNSCC is increasing, making it an important public health concern. Tumor resistance to contemporary treatments, namely, chemo- and radiotherapy, and the recurrence of the primary tumor after its surgical removal cause huge problems for patients. Despite recent improvements in these treatments, the 5-year survival rate is still relatively low. HNSCCs may develop local lymph node metastases and, in the most advanced cases, also distant metastases. A key process associated with tumor progression and metastasis is epithelial-mesenchymal transition (EMT), when poorly motile epithelial tumor cells acquire motile mesenchymal characteristics. These transition cells can invade different adjacent tissues and finally form metastases. EMT is governed by various transcription factors, including the best-characterized TWIST1 and TWIST2, SNAIL, SLUG, ZEB1, and ZEB2. Here, we highlight the current knowledge of the process of EMT in HNSCC and present the main protein markers associated with it. This review focuses on the transcription factors related to EMT and emphasizes their role in the resistance of HNSCC to current chemo- and radiotherapies. Understanding the role of EMT and the precise molecular mechanisms involved in this process may help with the development of novel anti-cancer therapies for this type of tumor.