RESUMO
Growth factorindependent 1 (GFI1) has been reported to serve a vital role in hematopoietic development. However, the function and molecular mechanism of GFI1 in esophageal squamous cell carcinoma (ESCC) remains unknown. In the present study, the biological functions and the molecular mechanism of the effects of GFI1 in ESCC were analyzed. The results demonstrated that GFI1 expression levels were significantly upregulated in ESCC compared with those in normal esophageal tissues. Knockdown of GFI1 using small interfering RNA suppressed ESCC cell proliferation and migration. Furthermore, GFI1 enhanced STAT3 and NFκB signaling by inhibiting the expression of suppressor of cytokine signaling 1 (SOCS1) in ESCC cells. Taken together, the results of the present study demonstrated that GFI1 promoted the proliferation and migration of ESCC cells via inhibition of SOCS1 expression. These results suggested that GFI1 may be a valuable target for ESCC therapy.
Assuntos
Movimento Celular/genética , Proliferação de Células/genética , Proteínas de Ligação a DNA/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Proteína 1 Supressora da Sinalização de Citocina/genética , Fatores de Transcrição/genética , Idoso , Linhagem Celular , Linhagem Celular Tumoral , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , NF-kappa B/genética , RNA Interferente Pequeno/genética , Fator de Transcrição STAT3/genética , Transdução de Sinais/genética , Regulação para Cima/genéticaRESUMO
Accumulating data indicate caspase-1 (CASP1), one of the inflammatory caspases, promotes hepatocellular carcinoma (HCC) progression in tumor proliferation, invasion, EMT phenotype and sorafenib resistance. However, the molecular basis of regulating caspase-1 expression and caspase-1/IL1B (interleukin-1ß) pathway in HCC remains unclear. Here, we demonstrated the novel interplay between caspase-1/IL1B activation and cluster differentiation 44 standard isoform (CD44s) in HCC. In this study, we observed that CD44s is responsible for caspase-1/IL1B activation both in HCC tissues and five HCC cell lines. In normoxia conditions, CD44s knockdown repressed the activation of caspase-1/IL1B via stimulating AMPK-mediated autophagy. Moreover, our data suggested that p62-induced autophagic degradation of caspase-1 accounted for caspase-1/IL1B inactivation in CD44s deficient cells. Administration of recombinant human IL1B could rescue impaired proliferation, invasion, and EMT phenotype in CD44s deficient HCC cells. Lastly, hypoxia-mediated caspase-1/IL1B overexpression could be abolished by CD44s downregulation through decreasing HIF1A and enhancing autophagic activity. Overall, targeting CD44s is a novel inhibitory mechanism of caspase-1/IL1B expression, both in normoxia and hypoxia conditions.
