Open AccessA double‐edged sword: The world according to Capicua in cancer
Author(s) -
Tanaka Miwa,
Yoshimoto Toyoki,
Nakamura Takuro
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13413
Subject(s) - cancer research , biology , gene , carcinogenesis , downregulation and upregulation , receptor tyrosine kinase , tyrosine kinase , phenotype , signal transduction , mapk/erk pathway , transcription factor , cancer , lung cancer , genetics , medicine , pathology
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.