Targeting Sphingosine-1-Phosphate Axis in Obesity-Promoted Breast Cancer

Abstract

Obesity, which induces low-grade inflammation, is a known risk factor for worse prognosis in many cancers including breast. We found that sphingosine-1-phosphate (S1P) produced by sphingosine kinases (SphKs) plays a critical role in obesity-related inflammation and breast cancer. Obesity increased S1P in the tumor microenvironment, as well as in the primary tumors. FTY720, a functional antagonist of S1PR1, dramatically decreased cancer progression by reducing expressions of SphK1 and S1PR1, and inflammatory cytokines including IL-6. Our results suggest a critical role for S1P in obesity-related inflammation and FTY720, an S1P axis inhibitor, appears to be a promising treatment for breast cancer in the obese condition, could be due to its effect on reactivate ERa expression and sensitize breast cancer cells to tamoxifen therapy.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2016
Accession Number
ADA636997

Entities

People

  • Dorit Avni

Organizations

  • Virginia Commonwealth University

Tags

DTIC Thesaurus Topics

  • Biochemistry
  • Biological Sciences
  • Blood
  • Breast Cancer
  • Cancer
  • Chemistry
  • Cytokines
  • Diseases And Disorders
  • Inflammation
  • Inhibitors
  • Laser Therapy
  • Molecular Biology
  • Neoplasms
  • Peptide Growth Factors
  • Proteins
  • Students
  • Therapy

Fields of Study

  • Biology

Readers

  • Allergy and Immunology.
  • Oncology (Cancer Research).