SFRP1 in Skin Tumor Initiation and Cancer Stem Cell Regulation with Potential Implications in Epithelial Cancers

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Raghava R Sunkara1, Rahul M Sarate2, Priyanka Setia2

  • 1Stem Cell Biology Group, Waghmare Lab, Cancer Research Institute, Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra 410210, India; Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400085, India.

Stem Cell Reports
|January 14, 2020
PubMed

Insights

Secreted frizzled-related protein 1 (SFRP1) downregulation promotes cancer stem cell (CSC) growth and tumor initiation. SFRP1 and SOX-2 show an inverse correlation in epithelial cancers, suggesting prognostic potential.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Stem Cell Research

Background:

  • Wnt signaling pathways regulate cancer stem cells (CSCs), but mechanisms are unclear.
  • SFRP1, a Wnt inhibitor, is downregulated in cancers, yet its role in tumor initiation and CSCs is unexplored.

Purpose of the Study:

  • To investigate the role of SFRP1 in tumor initiation and CSC regulation.
  • To explore the relationship between SFRP1 and SOX-2 in epithelial cancers.

Main Methods:

  • Utilized a skin carcinogenesis model in Sfrp1 knockout mice.
  • Performed expression profiling on Sfrp1 knockout CSCs.
  • Validated SFRP1 and SOX-2 expression in human cancer tissues (skin, head and neck, breast).

Main Results:

  • Sfrp1 knockout mice exhibited early tumor initiation and increased CSC tumorigenic potential.
  • Sfrp1 knockout CSCs showed upregulated genes in epithelial-mesenchymal transition, stemness, proliferation, and metastasis.
  • An inverse correlation between SFRP1 downregulation and SOX-2 upregulation was observed in human epithelial cancers.

Conclusions:

  • SFRP1 deficiency promotes tumor initiation and enhances CSCs' tumorigenic potential.
  • The inverse correlation between SFRP1 and SOX-2 in epithelial cancers may serve as a prognostic marker.
Keywords:
CSCsEMTHNSCCSfrp1 (secreted frizzled-related protein)cancer stem cellsepithelial cancerepithelial to mesenchymal transitionhead and neck squamous cell carcinomaskin squamous cell carcinomatumorigenic potential

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