Tumor suppressive role of CELF2 in skin tumorignesis
To investigate the function of CELF2 in non-melanoma skin cancer, we performed immunofluorescence staining studies and found lower CELF2 expression in human squamous cell carcinoma (SCC) tumors than in adjacent normal skin. CELF2 expression was also downregulated during both ultraviolet light- and chemical-induced skin tumorigenesis in mice, suggesting that CELF2 loss might promote skin cancer development. By using shRNA-mediated knockdown (KD) of CELF2 expression, we showed that CELF2 deficiency significantly increased SCC cell proliferation and colony growth in vitro and increased SCC tumor growth in a xenograft mouse model. Although control SCC cells were sensitive to anticancer drugs such as doxorubicin, CELF2-KD SCC cells were resistant to drug-induced tumor growth retardation. Through RNA-seq analysis, we identified that CELF2 loss led to activation of KRT80 and GDF15, which could confer growth and survival advantages to CELF2-deficient SCC cells. Overall design: We used cultured human SCC13 cells, mouse models, and clinical samples to analyze the function of CELF2 in skin tumorigenesis.