NOV 18, 2020 9:43 AM PST

Could Targeting the Proteasome be Effective Against Cancer?

WRITTEN BY: Jasper Cantrell

One of the trickiest things about anti-cancer drug design is targeting. Today, most drugs on the market target critical cell cycle or cell surface proteins, with new research identifying new targets every day.

In a new study out of the University of Toyama in Japan, a team conducted a screen and identified a possible protein target for cancer therapeutics. This target, called PMSD14, was tied to something called the proteasome, which has been on researchers’ radar for potential cancer therapeutics for a while now.

The proteasome is the primary protein disposal tool in most cells. An old or defective protein is tagged with something called ubiquitin, which targets that protein to the proteasome. The proteasome then shreds it into small pieces. The protein that the team identified is called PSMD14, which is responsible for un-tagging ubiquitinated proteins. It has also been linked to cancer in other studies.

The study first identified PSMD14 as a promoter of melanoma growth. The team then attempted to figure out the mechanism in which it worked. They analyzed genes that correlated one way or another with PSMD14’s loss. The team then examined how PSMD14 loss in melanoma cells affected growth and metastatic characteristics.

They began by knocking out the PSMD14 gene in a melanoma cell line. A previous study pointed to this knockout affecting cell cycle inhibitor proteins p21 and RB. The cell cycle is how cells grow and divide, so its inhibition effectively kills a cell. Indeed, PSMD14 knockout upregulated p21 expression and activated RB. Therefore, inhibiting PSMD14 with a drug could activate these two cell cycle inhibitors and impair melanoma growth.

The proteasome presents an interesting but complex target for anti-cancer therapeutics. This study shines a light on not the proteasome but on one of its assisting proteins. PSMD14 knockout in melanoma results in the activation and upregulation of CDK inhibitors RB and p21, which impairs the growth of melanoma cells in vitro. Targeting PSMD14 would allow scientists to selectively target the proteasome without inducing catastrophic dysfunction, although far more research needs to be done to ensure it would work.

The study concludes, “Although we identified PSMD14 as a molecular target for melanoma, there is currently no available drug targeting PSMD14. As the disturbance of proteasome function by PSMD14 knockdown may affect melanoma growth, proteasome inhibitors, including bortezomib, may be attractive drugs for melanoma.”

Sources: Nature Scientific Reports, Myeloma UK

About the Author
  • Hey everyone! My name is Jasper and, considering I am pretty new here to Labroots, I figured I would introduce myself. I received my bachelor’s from the University of California at Riverside back in 2016. I started off my career a few years ago with a job at a University over in New York, before moving over into the industry. I'm happy to be writing content for Labroots, and I hope you enjoy it!
You May Also Like
SEP 11, 2020
Cancer
Targeting Senescence in the Peripheral Nervous System to Fight Toxicity
SEP 11, 2020
Targeting Senescence in the Peripheral Nervous System to Fight Toxicity
Chemotherapy is a life-saving discovery for cancer patients. One of its biggest drawbacks is the toxicity that comes wit ...
SEP 28, 2020
Cancer
A New Transcriptomics Program in the Works Glioma Diagnosis
SEP 28, 2020
A New Transcriptomics Program in the Works Glioma Diagnosis
The future of medicine is “personalized healthcare.” However, testing remains a critical hurdle researcher&r ...
OCT 26, 2020
Cancer
Investigating the Receptor Protein FPR1 in Brain Cancer
OCT 26, 2020
Investigating the Receptor Protein FPR1 in Brain Cancer
Amongst the more common targets for cancer therapies are cell surface receptors. These receptors are proteins – us ...
NOV 18, 2020
Genetics & Genomics
Choosing an NGS workflow: What are you looking for?
NOV 18, 2020
Choosing an NGS workflow: What are you looking for?
  It’s easy to be overwhelmed by the number of workflows that are available for NGS. How do you choose? While ...
NOV 07, 2020
Cancer
Newly identified biomarker sheds light on antiangiogenic drug responses
NOV 07, 2020
Newly identified biomarker sheds light on antiangiogenic drug responses
A study published last week in the journal EMBO Molecular Medicine provides insight into the molecular mechanisms t ...
NOV 20, 2020
Cancer
How does tissue geometry influence cancer cellular migration?
NOV 20, 2020
How does tissue geometry influence cancer cellular migration?
A team of researchers led by UC Santa Barbara's Distinguished Professor Denise Montell has recently published new fi ...
Loading Comments...