A novel study on the regulation of Myc entitled “CSN6 drives carcinogenesis by positively regulating Myc stability” was published in Nature Communications by Jian Chen, part of Dr. Mong-Hong Lee’s group in the Department of Molecular and Cellular Oncology at The University of Texas MD Anderson Cancer Center.
In this study, the authors showed that Myc is a target of the COP9 signalosome (CSN) subunit 6 (CSN6)-Cullin signaling axis, and that CSN6 is a positive regulator of Myc. Myc is a proto-oncogene, or master cancer gene, that stimulates tumor growth in a series of cancers including breast, lung, colon, brain, skin, leukemia, prostate, pancreas, stomach and bladder. Myc suffers ubiquitination, a process were ubiquitin molecules are attached to a protein either to lead to their degradation, alter their cellular location, or affect their activity, and promote or prevent protein interactions by Cullin-RING ubiquitin ligases (CRLs). The COP9 signalosome (CSN) controls neddylation, a process similar to ubiquitination, of Cullin in CRL. However, the mechanistic link between Cullin neddylation and Myc ubiquitination/degradation is not well understood. They found that overexpression of CSN6 led to aberrant expression of genes targeted by Myc and is a common feature observed in human cancers. Altogether, these results provide new insights into the overexpression of CSN6 and Myc stabilization/activation during tumorigenesis.
“We have discovered that CSN6 is a strong oncogene that is frequently overexpressed and significantly speeds up tumor growth in many types of cancer,” said Dr. Lee, in a press release. “Furthermore, CSN6 also affects the expression of Myc in tumors.”
Dr. Lee said that their findings are crucial since targeting Myc is a very difficult task due to its unique protein structure. Although it has been studied for decades, no effective inhibitor for Myc has been successfully developed. Notably, the research team found that the inhibition of CSN6 rapidly destabilized Myc inhibiting significantly metastasis and tumor growth.
“This has the potential to unlock a promising and completely new door to effectively eliminating tumors and suppressing cancers that overexpress Myc,” concluded Dr. Lee.
This study was funded by the National Institutes of Health, the Fidelity Foundation and the Susan G. Komen Breast Cancer Foundation.