Biomarker Associated With Poor Survival Among Colorectal Cancer Patients

Biomarker Associated With Poor Survival Among Colorectal Cancer Patients

August 20, 2015

A protein called CSN6 has been found to be correlated with poor survival among patients with colorectal cancer.

A protein called CSN6 has been found to be correlated with poor survival among patients with colorectal cancer. In addition, cetuximab may be an agent that inhibits CSN6 expression and tumor growth, according to a study published in the August 10, 2015 issue of Cancer Cell.1

The study suggests CSN6, a subunit of a protein complex known as COP9 signalsome, is overexpressed in colorectal cancer tissue samples. The finding could be significant because it points potential alternative treatment strategies for colorectal cancer.

“CSN6 is a biomarker that is elevated in colon cancer and leads to worse recurrence-free survival,” said study investigator Mong-Hong Lee, PhD, professor of Molecular and Cellular Oncology at The University of Texas MD Anderson Cancer Center in Dallas. “This occurs when CSN6 is deregulated through a series of cellular signaling pathways.”2

The biomarker is normally regulated through signaling pathways EGFR (epidermal growth factor receptor) and ERK (extracellular signal-regulated kinase). When CSN6 is overexpressed via ERK2, it can lead to deregulation of another protein (beta-catenin), a transcription factor known to be linked to cancer development. The researchers found that deregulation of CSN6 by ERK2 resulted in stabilization and activation of beta-catenin, which is important for colorectal cancer development.  The researchers also were able to further define the mechanism by which beta-catenin is regulated in this cancer. 

The study demonstrated that ERK2 binds directly to CSN6 and phosphorylates CSN6 at Ser148 to stabilize CSN6. The researchers also found that CSN6-mediated β-catenin stabilization appears to involve β-Trcp downregulation, and the inhibition of ERK2 by cetuximab may have the potential to inhibit CSN6 expression and tumor growth. In their experiments, they found that tissue samples taken from colorectal cancer patients showed that inhibiting CSN6 stability with cetuximab reduced colon cancer growth.

“The molecular alterations in colorectal cancer have been studied extensively,” said Dr. Lee. “However, a more detailed picture of the pathways deregulated in this cancer has yet to emerge. Defining those molecular alterations can help guide treatment and improve clinical care.”

Currently, the standard treatment for colorectal cancer patients at high risk of developing recurrent or metastatic cancer includes surgery, chemotherapy, and/or targeted therapies.  Dr. Lee said there is an acute need to better identify the molecular pathways associated with recurrent or metastatic colorectal cancer.

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