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Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics
11:28

Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics

Published on: May 11, 2016

A role of sphingosine kinase 1 in head and neck carcinogenesis

Keisuke Shirai1, Tatsuya Kaneshiro, Masayuki Wada

  • 1Department of Hematology/Oncology, Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.

Cancer Prevention Research (Philadelphia, Pa.)
|January 7, 2011
PubMed

Insights

Sphingosine kinase 1 (SphK1) is overexpressed in head and neck squamous cell carcinoma (HNSCC). Inhibiting SphK1/sphingosine-1-phosphate (S1P) signaling significantly prevented HNSCC development in a mouse model, suggesting a new therapeutic strategy.

Area of Science:

  • Oncology
  • Biochemistry
  • Molecular Biology

Background:

  • Head and neck squamous cell carcinoma (HNSCC) is a lethal cancer requiring novel therapeutic targets.
  • Bioactive sphingolipids, like sphingosine-1-phosphate (S1P) and its generating enzyme sphingosine kinase 1 (SphK1), are implicated in tumor growth and carcinogenesis.

Purpose of the Study:

  • To investigate the role of SphK1/S1P signaling in HNSCC development and progression.
  • To determine if SphK1 is a potential therapeutic target for HNSCC.

Main Methods:

  • Immunohistochemical analysis of SphK1 expression in human HNSCC tissues and normal controls.
  • Utilized a 4-nitroquinoline-1-oxide (4-NQO)-induced HNSCC mouse model comparing wild-type and SphK1 knockout (KO) mice.

Main Results:

  • SphK1 was overexpressed in all tested HNSCC tumor samples.
  • Genetic SphK1 deficiency significantly reduced HNSCC incidence, multiplicity, and tumor volume in the 4-NQO model.
  • SphK1 loss was associated with decreased cell proliferation, increased cleaved caspase 3, and reduced phospho-AKT levels.

Conclusions:

  • SphK1/S1P signaling plays a critical role in HNSCC carcinogenesis.
  • Targeting SphK1/S1P represents a promising novel strategy for HNSCC chemoprevention and treatment.

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