A double-edged sword: The world according to Capicua in cancer
| Autor: | Takuro Nakamura, Miwa Tanaka, Toyoki Yoshimoto |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Cancer Research CIC‐DUX4 Review Article Biology medicine.disease_cause Receptor tyrosine kinase 03 medical and health sciences Downregulation and upregulation Neoplasms medicine Animals Humans Transcription factor Genetics round cell sarcoma Cancer General Medicine medicine.disease Phenotype oligodendroglioma Unsolicited Review Article Repressor Proteins 030104 developmental biology Oncology Capicua/CIC RTK/RAS/MAPK pathway Cancer research biology.protein Signal transduction Carcinogenesis |
| Zdroj: | Cancer Science |
| ISSN: | 1349-7006 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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