Making heads or tails - the emergence of capicua (CIC) as an important multifunctional tumour suppressor.

Capicua, encoded by the gene CIC, is an evolutionarily conserved high-mobility group-box transcription factor downstream of the receptor tyrosine kinase and mitogen-activated protein kinase pathways. It was initially discovered and studied in Drosophila. Recurrent mutations in CIC were first identified in oligodendroglioma, a subtype of low-grade glioma. Subsequent studies have identified CIC aberrations in multiple types of cancer and have established CIC as a potent tumour suppressor involved in regulating pathways related to cell growth and proliferation, invasion and treatment resistance. The most well-known and studied targets of mammalian CIC are the oncogenic E-Twenty Six transcription factors ETV1/4/5, which have been found to be elevated in cancers with CIC aberrations. Here, we review the role of CIC in normal mammalian development, oncogenesis and tumour progression, and the functional interactors that mediate them.