Understanding Epithelial-Mesenchymal Transition may Reveal Novel Therapeutic Targets for Oral Squamous Cell Carcinoma

Hidayatullah      G. Munshi; M. Sharon      Stack

Abstract

Worldwide more than 350,000 patients will be diagnosed with oral cancer this year; however, the survival of patients with oral cancer has not changed significantly over the last 30 years. Recent reports have demonstrated that epithelial-mesenchymal transition (EMT) not only contributes to cancer cell invasion and metastasis but it is also associated with treatment resistance. In this review, we will examine the data demonstrating the role of EMT in oral cancer and the extent to which it contributes to poor response to current therapeutic modalities. We will also examine the interplay between EMT and microRNAs and review the role of microRNAs in modulating resistance of oral cancer cells to current therapeutic modalities. Similarly, we will review how EMT contributes to the generation and maintenance of stem cells and examine the role of stem cells in oral cancer recurrence and in modulating treatment resistance. Finally, we will examine how EMT is involved in fibrosis, which can limit delivery of therapeutic agents to cancer cells. Overall, this review will summarize our understanding of how EMT contributes to oral cancer progression and identify additional therapeutic targets that may help to reduce the morbidity and mortality associated with oral cancer.

Keywords: Epithelial-mesenchymal transition, microRNA, stem cells, fibrosis, oral cancer, treatment resistance, chemotherapy, E-cadherin, metalloproteinas, cytokine interleukin