The Role of Exosomes in Epithelial-to-Mesenchymal Transition and Cell Functional Properties in Head and Neck Cancer

Exosomes are nanosized vesicles that are produced in normal and cancer cells, promoting intracellular communication. In head and neck cancer (HNC), exosomes are involved inmany undesirable events of cancer development and progression, including angiogenesis, tumormicroenvironment (TME) remodeling, invasion, epithelial-to-mesenchymal transition (EMT), metastasis, extracellular matrix (ECM) degradation, and drug resistance. Exosomes are involved in altering the signaling pathways in recipient cells by the cargoes they carry. Proteins, lipids, and nucleic acids such as DNA fragments and RNAs (i.e., mRNAs, miRNAs, and long non-coding RNAs) are carried in the exosomes to promote cell communication. EMT is a critical cellular process in which epithelial cells are forced to becomemesenchymal cells by the actions of SNAIL/SLUG, TWIST, and ZEB family transcription factors carried in exosomes that facilitate metastasis. In this critical review, we focused on exosome biogenesis, their cargoes, and their involvement in EMT induction andmetastasis during HNC. Insights into exosome isolation and characterization, as well as their key role in ECM remodeling and degradation, are also presented and critically discussed. More importantly, this article addresses the role of exosomes in HNC and drug resistance induced in drug-sensitive cancer cells. In addition, exosomes have a great potential to be used as diagnostic and therapeutic tools. A better understanding on exosome biogenesis, composition, and functions in HNC will aid in developing novel therapeutic strategies to treat HNC, overcome therapy resistance, and avoid metastasis, which is a significant cause of cancer death.

Automated summary

Exosomes are nanosized vesicles produced by cells that play important roles in head and neck cancer development and metastasis by altering signaling pathways in recipient cells through the cargoes they carry. This article focuses on exosome biogenesis, their cargoes, and their involvement in epithelial-to-mesenchymal transition (EMT) induction and metastasis in head and neck cancer. It also discusses the key role of exosomes in extracellular matrix remodeling and degradation, and their potential as diagnostic and therapeutic tools.