Journal
CELL CYCLE
Volume 17, Issue 6, Pages 702-711Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15384101.2018.1450029
Keywords
CIC; Ras signaling; T-ALL; mouse models; Etv4
Categories
Funding
- Fundacio La Marato de TV3 [20131730/1]
- European Research Council [ERC-AG/250297-RAS AHEAD, ERC-AG/695566-THERACAN]
- Autonomous Community of Madrid [S2011/BDM-2470/ONCOCYCLE]
- Foundation of the Asociacion Espanola contra el Cancer (AECC) [GC16173694BARB]
- Spanish Ministry of Economy and Competitiveness [SAF2014-59864-R, BFU2014-52863-P]
- AXA Research Fund
- Programa de Formacion de Personal Investigator (FPI) of the Spanish Ministry of Economy and Competitiveness
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The transcriptional repressor Capicua (CIC) has emerged as an important rheostat of cell growth regulated by RAS/MAPK signaling. Cic was originally discovered in Drosophila, where it was shown to be inactivated by MAPK signaling downstream of the RTKs Torso and EGFR, which results in signal-dependent responses that are required for normal cell fate specification, proliferation and survival of developing and adult tissues. CIC is highly conserved in mammals, where it is also negatively regulated by MAPK signaling. Here, we review the roles of CIC during mammalian development, tissue homeostasis, tumor formation and therapy resistance. Available data indicate that CIC is involved in multiple biological processes, including lung development, liver homeostasis, autoimmunity and neurobehavioral processes. Moreover, CIC has been shown to be involved in tumor development as a tumor suppressor, both in human as well as in mouse models. Finally, several lines of evidence implicate CIC as a determinant of sensitivity to EGFR and MAPK pathway inhibitors, suggesting that CIC may play a broader role in human cancer than originally anticipated.
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