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.

Epithelial–mesenchymal plasticity in cancer: signaling pathways and therapeutic targets

“… 13 Increasing evidence suggests that both EMT‐TFs such as Snail and Twist as well as EMT‐related signaling pathways including TGF‐β, Wnt, and Notch are correlated with the therapeutic resistance. 5 , 210 , 211 Here, we summarize the EMP‐induced resistance to chemotherapy and targeted therapy as well as the implications of EMP in immune evasion and immunotherapy resistance.…”

“… 4 The signals form the microenvironment for example transforming growth factor (TGF)‐β, epigenetically orchestrate the phenotypic switch of tumor cells via modulating the expression of a range of transcription factors (TFs), including Snail, ZEB, and Twist, which impact on the expression of epithelial genes or mesenchymal genes. 5 With the changes in cellular phenotypes, tumor cells acquire different malignant features to adapt to the stress conditions. During tumor progression, tumor cells with EMP will be influenced by dynamic and stressful microenvironmental factors, such as the primary site with hypoxia, inflammation, remodeled extracellular matrix (ECM), and various stromal cells, the vascular environment with immune surveillance and the premetastatic site with extracellular vesicles (EVs), all of which may impact the EMP states of tumor cells via regulating EMP‐related signaling pathways.…”