A double-edged sword: The world according to Capicua in cancer.
Miwa TanakaToyoki YoshimotoTakuro NakamuraPublished in: Cancer science (2017)
CIC/Capicua is an HMG-box transcription factor that is well conserved during evolution. CIC recognizes the T(G/C)AATG(A/G)A sequence and represses its target genes, such as PEA3 family genes. The receptor tyrosine kinase/RAS/MAPK signals downregulate CIC and relieves CIC's target genes from the transrepressional activity; CIC thus acts as an important downstream molecule of the pathway and as a tumor suppressor. CIC loss-of-function mutations are frequently observed in several human neoplasms such as oligodendroglioma, and lung and gastric carcinoma. CIC is also involved in chromosomal translocation-associated gene fusions in highly aggressive small round cell sarcoma that is biologically and clinically distinct from Ewing sarcoma. In these mutations, PEA3 family genes and other important target genes are upregulated, inducing malignant phenotypes. Downregulation of CIC abrogates the effect of MAPK inhibitors, suggesting its potential role as an important modifier of molecular target therapies for cancer. These data reveal the importance of CIC as a key molecule in signal transduction, carcinogenesis, and developing novel therapies.
Keyphrases
- genome wide
- genome wide identification
- transcription factor
- tyrosine kinase
- signaling pathway
- bioinformatics analysis
- papillary thyroid
- dna methylation
- copy number
- epidermal growth factor receptor
- oxidative stress
- endothelial cells
- stem cells
- gene expression
- squamous cell
- mesenchymal stem cells
- cell proliferation
- big data
- bone marrow
- electronic health record