Suppression of type I interferon signaling proteins is an early event in squamous skin carcinogenesis

John L Clifford1, Eugene Walch, Xiulan Yang

  • 1Departments of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. jclifford@mdanderson.org

Abstract

Insights

Suppressed expression of IFN-stimulated gene factor 3 (ISGF-3) proteins, key to IFN-alpha signaling, is an early event in skin carcinogenesis. This occurs in both actinic keratosis and squamous cell carcinoma (SCC).

Area of Science:

  • Oncology
  • Immunology
  • Dermatology

Background:

  • Interferon (IFN)-based therapy shows efficacy in treating squamous cell carcinoma (SCC) of the skin.
  • IFN-stimulated gene factor 3 (ISGF-3) proteins are critical mediators of IFN-alpha signaling.
  • Previous studies indicated potential suppression of ISGF-3 proteins in skin SCC.

Purpose of the Study:

  • To investigate the timing of ISGF-3 protein suppression during squamous skin carcinogenesis.
  • To compare ISGF-3 expression in premalignant actinic keratosis and normal skin.

Main Methods:

  • Immunohistochemical staining was used to assess ISGF-3 protein expression.
  • Biopsies from patients with actinic keratosis and matched normal skin were analyzed.
  • Expression levels were compared between premalignant lesions, SCC, and normal skin.

Main Results:

  • A significant decrease in one or more ISGF-3 proteins was observed in 76% of actinic keratosis patients.
  • Suppression of ISGF-3 proteins was confirmed in 67% of skin SCC patients.
  • These findings suggest a pattern of declining ISGF-3 protein expression during skin cancer development.

Conclusions:

  • Suppressed expression of ISGF-3 proteins is likely an early event in skin carcinogenesis.
  • Reduced responsiveness to endogenous IFN due to ISGF-3 suppression may play a role in cancer development.
  • These findings highlight the importance of IFN signaling pathways in skin premalignancy and SCC.

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