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Emerging role of sphingosine-1-phosphate signaling in head and neck squamous cell carcinoma

Authors Nema R, Vishwakarma S, Agarwal R, Panday RK, Kumar A

Received 6 November 2015

Accepted for publication 24 March 2016

Published 31 May 2016 Volume 2016:9 Pages 3269—3280

DOI https://doi.org/10.2147/OTT.S99989

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Wei An

Peer reviewer comments 5

Editor who approved publication: Dr Faris Farassati


Rajeev Nema,1 Supriya Vishwakarma,1 Rahul Agarwal,2 Rajendra Kumar Panday,3 Ashok Kumar1

1Department of Biochemistry, All India Institute of Medical Sciences Bhopal, Bhopal, 2Jawaharlal Nehru Cancer Hospital & Research Centre, 3Navodaya Cancer Hospital, Indrapuri, Bhopal, India

Abstract: Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent cancer type, with an annual incidence of approximately half a million people worldwide. It has a high recurrence rate and an extremely low survival rate. This is due to limited availability of effective therapies to reduce the rate of recurrence, resulting in high morbidity and mortality of patients with advanced stages of the disease. HNSCC often develops resistance to chemotherapy and targeted drug therapy. Thus, to overcome the problem of drug resistance, there is a need to explore novel drug targets. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid involved in inflammation, tumor progression, and angiogenesis. S1P is synthesized intracellularly by two sphingosine kinases (SphKs). It can be exported to the extracellular space, where it can activate a family of G-protein-coupled receptors. Alternatively, S1P can act as an intracellular second messenger. SphK1 regulates tumor progression, invasion, metastasis, and chemoresistance in HNSCC. SphK1 expression is highly elevated in advanced stage HNSCC tumors and correlates with poor survival. In this article, we review current knowledge regarding the role of S1P receptors and enzymes of S1P metabolism in HNSCC carcinogenesis. Furthermore, we summarize the current perspectives on therapeutic approaches for targeting S1P pathway for treating HNSCC.

Keywords: head and neck squamous cell carcinoma, HNSCC, oral squamous cell carcinoma, OSCC, sphingosine-1-phosphate, S1P, sphingosine kinase 1, SphK1, S1P receptor, sphingolipid

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