The Impact of Sphingosine Kinase-1 in Head and Neck Cancer

Head and neck squamous cell carcinoma (HNSCC) has a high reoccurrence rate and an extremely low survival rate. There is limited availability of effective therapies to reduce the rate of recurrence, resulting in high morbidity and mortality of advanced cases. Late presentation, delay in detection of...

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Main Authors: Toshihiko Kawamori, Kayoko Iino, Yoshiko Shimizu, Hideki Furuya, Paulette M. Tamashiro
Format: Article
Language:English
Published: MDPI AG 2013-08-01
Series:Biomolecules
Subjects:
Online Access:http://www.mdpi.com/2218-273X/3/3/481
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author Toshihiko Kawamori
Kayoko Iino
Yoshiko Shimizu
Hideki Furuya
Paulette M. Tamashiro
author_facet Toshihiko Kawamori
Kayoko Iino
Yoshiko Shimizu
Hideki Furuya
Paulette M. Tamashiro
author_sort Toshihiko Kawamori
collection DOAJ
description Head and neck squamous cell carcinoma (HNSCC) has a high reoccurrence rate and an extremely low survival rate. There is limited availability of effective therapies to reduce the rate of recurrence, resulting in high morbidity and mortality of advanced cases. Late presentation, delay in detection of lesions, and a high rate of metastasis make HNSCC a devastating disease. This review offers insight into the role of sphingosine kinase-1 (SphK1), a key enzyme in sphingolipid metabolism, in HNSCC. Sphingolipids not only play a structural role in cellular membranes, but also modulate cell signal transduction pathways to influence biological outcomes such as senescence, differentiation, apoptosis, migration, proliferation, and angiogenesis. SphK1 is a critical regulator of the delicate balance between proliferation and apoptosis. The highest expression of SphK1 is found in the advanced stage of disease, and there is a positive correlation between SphK1 expression and recurrent tumors. On the other hand, silencing SphK1 reduces HNSCC tumor growth and sensitizes tumors to radiation-induced death.  Thus, SphK1 plays an important and influential role in determining HNSCC proliferation and metastasis. We discuss roles of SphK1 and other sphingolipids in HNSCC development and therapeutic strategies against HNSCC.
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spelling doaj.art-e1fe6cc3384e4fe081ed4d2cba24bb602022-12-22T03:41:09ZengMDPI AGBiomolecules2218-273X2013-08-013348151310.3390/biom3030481The Impact of Sphingosine Kinase-1 in Head and Neck CancerToshihiko KawamoriKayoko IinoYoshiko ShimizuHideki FuruyaPaulette M. TamashiroHead and neck squamous cell carcinoma (HNSCC) has a high reoccurrence rate and an extremely low survival rate. There is limited availability of effective therapies to reduce the rate of recurrence, resulting in high morbidity and mortality of advanced cases. Late presentation, delay in detection of lesions, and a high rate of metastasis make HNSCC a devastating disease. This review offers insight into the role of sphingosine kinase-1 (SphK1), a key enzyme in sphingolipid metabolism, in HNSCC. Sphingolipids not only play a structural role in cellular membranes, but also modulate cell signal transduction pathways to influence biological outcomes such as senescence, differentiation, apoptosis, migration, proliferation, and angiogenesis. SphK1 is a critical regulator of the delicate balance between proliferation and apoptosis. The highest expression of SphK1 is found in the advanced stage of disease, and there is a positive correlation between SphK1 expression and recurrent tumors. On the other hand, silencing SphK1 reduces HNSCC tumor growth and sensitizes tumors to radiation-induced death.  Thus, SphK1 plays an important and influential role in determining HNSCC proliferation and metastasis. We discuss roles of SphK1 and other sphingolipids in HNSCC development and therapeutic strategies against HNSCC.http://www.mdpi.com/2218-273X/3/3/481sphingolipidsSphK1S1Phead and neck cancerinvasion and proliferation
spellingShingle Toshihiko Kawamori
Kayoko Iino
Yoshiko Shimizu
Hideki Furuya
Paulette M. Tamashiro
The Impact of Sphingosine Kinase-1 in Head and Neck Cancer
Biomolecules
sphingolipids
SphK1
S1P
head and neck cancer
invasion and proliferation
title The Impact of Sphingosine Kinase-1 in Head and Neck Cancer
title_full The Impact of Sphingosine Kinase-1 in Head and Neck Cancer
title_fullStr The Impact of Sphingosine Kinase-1 in Head and Neck Cancer
title_full_unstemmed The Impact of Sphingosine Kinase-1 in Head and Neck Cancer
title_short The Impact of Sphingosine Kinase-1 in Head and Neck Cancer
title_sort impact of sphingosine kinase 1 in head and neck cancer
topic sphingolipids
SphK1
S1P
head and neck cancer
invasion and proliferation
url http://www.mdpi.com/2218-273X/3/3/481
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