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Updated: Jun 23, 2025

Cell Population Analyses During Skin Carcinogenesis
Published on: August 21, 2013
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.
Background:
CELF2 belongs to the CELF RNA-binding protein family and exhibits antitumor activity in various tumor models. Analysis of the pan-cancer TCGA database reveals that CELF2 expression strongly correlates with favorable prognosis among cancer patients. The function of CELF2 in nonmelanoma skin cancer has not been studied.
Methods:
We used shRNA-mediated knockdown (KD) of CELF2 expression in human squamous cell carcinoma (SCC) cells to investigate how CELF2 impacted SCC cell proliferation, survival, and xenograft tumor growth. We determined CELF2 expression in human SCC tissues and adjacent normal skin using immunofluorescence staining. Additionally, we investigated the changes in CELF2 and its target gene expression during UV-induced and chemical-induced skin tumorigenesis by western blotting.
Results:
CELF2 KD significantly increased SCC cell proliferation, colony growth, and SCC xenograft tumor growth in immunodeficient mice. CELF2 KD in SCC cells led to activation of KRT80 and GDF15, which can potentially promote cell proliferation and tumor growth. While control SCC cells were sensitive to anticancer drugs such as doxorubicin, SCC cells with CELF2 KD became resistant to drug-induced tumor growth retardation. Finally, we found CELF2 expression diminished during both UV- and chemical-induced skin tumorigenesis in mice, consistent with reduced CELF2 expression in human SCC tumors compared to adjacent normal skin.
Conclusion:
This study shows for the first time that CELF2 loss occurs during skin tumorigenesis and increases drug resistance in SCC cells, highlighting the possibility of targeting CELF2-regulated pathways in skin cancer prevention and therapies.
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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