Transcriptomic analysis of CIC and ATXN1L reveal a functional relationship exploited by cancer.
Derek WongKohl LounsburyAmy LumJungeun SongSusanna ChanVeronique LeBlancSuganthi ChittaranjanMarco MarraStephen YipPublished in: Oncogene (2018)
Aberrations in Capicua (CIC) have recently been implicated as a negative prognostic factor in a multitude of cancer types through activation of the MAPK signalling cascade and derepression of oncogenic ETS transcription factors. The Ataxin-family protein ATXN1L has previously been reported to interact with CIC in developmental and disease contexts to facilitate the repression of CIC target genes. To further investigate this relationship, we performed functional in vitro studies utilizing ATXN1LKO and CICKO human cell lines and characterized a reciprocal functional relationship between CIC and ATXN1L. Transcriptomic interrogation of the CIC-ATXN1-ATXN1L axis in low-grade glioma, prostate adenocarcinoma and stomach adenocarcinoma TCGA cohorts revealed context-dependent convergence of gene sets and pathways related to mitotic cell cycle and division. This study highlights the CIC-ATXN1-ATXN1L axis as a more potent regulator of the cell cycle than previously appreciated.
Keyphrases
- cell cycle
- transcription factor
- low grade
- cell proliferation
- prognostic factors
- genome wide
- papillary thyroid
- prostate cancer
- squamous cell carcinoma
- single cell
- high grade
- endothelial cells
- genome wide identification
- copy number
- signaling pathway
- squamous cell
- dna methylation
- pi k akt
- dna binding
- small molecule
- lymph node metastasis
- protein protein
- case control