Loss of CELF2 promotes skin tumorigenesis and increases drug resistance

Bindeshwar Sah1, Jasvinder Singh1, Yao Shen2

  • 1The Hormel Institute, University of Minnesota, Austin, MN, USA.

Abstract

Insights

Loss of CELF2 protein in skin cancer promotes tumor growth and drug resistance. Restoring CELF2 may offer new therapeutic strategies for squamous cell carcinoma (SCC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • CELF2 (CUG-BP and ETR-3-like protein 2) is an RNA-binding protein with known antitumor activity.
  • CELF2 expression correlates with better prognosis in pan-cancer analyses.
  • The role of CELF2 in nonmelanoma skin cancer remains uninvestigated.

Purpose of the Study:

  • To investigate the function of CELF2 in squamous cell carcinoma (SCC).
  • To determine the impact of CELF2 on SCC cell proliferation, survival, and tumor growth.
  • To explore CELF2's role in skin tumorigenesis and drug resistance.

Main Methods:

  • Utilized shRNA-mediated knockdown (KD) of CELF2 in human SCC cells.
  • Assessed SCC cell proliferation, colony formation, and xenograft tumor growth.
  • Examined CELF2 expression in human SCC tissues and mouse models of skin tumorigenesis via immunofluorescence and western blotting.

Main Results:

  • CELF2 KD significantly enhanced SCC cell proliferation, colony growth, and xenograft tumor growth.
  • CELF2 KD activated KRT80 and GDF15, potentially promoting proliferation and tumor growth.
  • CELF2 KD induced resistance to doxorubicin in SCC cells, while CELF2 expression decreased during skin tumorigenesis.

Conclusions:

  • CELF2 loss is associated with skin tumorigenesis and increased drug resistance in SCC.
  • Targeting CELF2-regulated pathways presents a potential strategy for skin cancer prevention and therapy.

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