Tetraspanin CD9: A friend or foe of head and neck cancer (Review)

Abstract

Head and neck cancers are diverse and complex diseases characterised by unregulated growth of tumour cells in various parts of the head and neck region, such as in the buccal mucosa, floor of the mouth, tongue, oropharynx, hypopharynx, oesophagus, nasopharynx and salivary glands. Partial or total glossectomy, radiation or chemotherapy greatly affect patient quality of life. However, even following treatment, patients may relapse. Nicotine‑derived nitrosamines and alcohol are the major etiological factors underlying this deadly disease. These compounds induce DNA damage that may lead to mutation in crucial genes, such as p53 and p21, which are important to regulate cell proliferation, thus leading to cancer. CD9 is a tetraspanin, which are a group of transmembrane proteins that have a role in cell motility and adhesion. The present review aimed to explore the role of CD9 in head and neck cancer. Epidermal growth factor receptor activity and cell proliferation are regulated by the CD9‑integrin/CD9‑transforming growth factor interaction. Hence, CD9 can play a dual role in various types of cancer.

Keywords: cell proliferation; head and neck squamous cell carcinoma; nicotine‑derived nitrosamines; tetraspanin; tobacco.

Figure 1.

Role of nicotine-derived compounds and alcohol in head and neck squamous cell carcinoma. NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; NNN, N'-nitrosonornicotine; ROS, reactive oxygen species; nAChR, nicotinic acetylcholine receptor.

Figure 2.

Biomarkers of HNSCC. HNSCC, head and neck squamous cell carcinoma; MMP, matrix metalloproteinase; miR, microRNA; PD-L1, programmed death ligand 1.

Figure 3.

Structure of tetraspanin CD9. It has a small and large extracellular loop and four transmembrane domains that span the plasma membrane.

Figure 4.

Interaction of CD9 with integrins and TGFα. TGFα, transforming growth factor α; ECM, extracellular matrix; EGFR, epidermal growth factor receptor.

Figure 5.

Interaction of CD9 with NF-κB, TNFα and caspase 3. TNFα, tumour necrosis factor α.

Figure 6.

Interaction of CD9 with integrins, TGFα and EGFR. Interaction with these proteins may promote or inhibit cancer progression, migration and invasion. TGFα, transforming growth factor α; EGFR, epidermal growth factor receptor; FAK, focal adhesion kinase; GEFs, guanidine exchanging factors; ADAM17, disintegrin and metalloprotease 17; PSI, plexin-semaphorin-integrin domain; P-, phosphorylated.