TRIM25 Promotes Capicua Degradation Independently of ERK in the Absence of ATXN1L
This week we profile a recent publication in BMC Biology from Derek
Wong and the laboratory of Dr. Stephen Yip (pictured) at BC Cancer.
Can you provide a brief overview of your lab’s current research focus?
The overall direction of the lab is translational neuro-oncology through multi-omic interrogation of clinical brain cancer specimens. The focus of this project is the study of Capicua (CIC) which is frequently disrupted in oligodendroglioma, and how this can mediate or promote cancer progression and contribute to the cancer biology. This work builds on the discovery of recurrent mutations of CIC in brain cancer as well as the follow-up mechanistic studies done in collaboration with the Marra lab at the BC Genome Sciences Centre.
What is the significance of the findings in this publication?
This publication broadens our understanding of the post-translational regulation of CIC which has now been implicated as a tumour suppressor in multiple cancer types, including glioma. In fact, CIC has been shown to mediate EGFR signalling as well as metastatic behaviour. It also delves into non-canonical CIC regulatory pathways and identifies a novel E3-ligase, TRIM25, which can regulate CIC function at a post-translational level.
What are the next steps for this research?
The next steps for this research would be to further the understanding of mechanisms and pathways, both canonical and non-canonical, that regulate CIC function and to determine if and how they can be leveraged in order to restore or maintain CIC’s tumour suppressor activity in cancers. Given its role in regulating EGFR signalling through the MAPK pathway, one potential avenue is its modulation to alter signalling events in oncogenesis and resistance to targeted therapeutics.
This work was funded by:
The BC Cancer Foundation.