Cancer stem cells don’t waste their time cleaning—low proteasome activity, a marker for cancer stem cell function

A population of stem-like cells in tumors, the so-called cancer stem cells (CSCs), are being held responsible for therapy resistance and tumor recurrence. In analogy with normal stem cells, CSCs possess the capacity of long term self-renewal and multilineage differentiation. CSCs are believed to be more resistant to various therapies compared to their differentiated offspring and therefore the cause of tumor relapse. Markers for CSCs have been identified using xenograft transplantation assays and lineage tracing in mouse models, however the specificity and validity of many of these markers is under debate. Recently, low proteasome activity has been postulated as a novel CSC marker. In several solid malignancies a small subset of low proteasomal activity cells with CSC characteristics were identified, suggesting that proteasomal activity might be a functional marker for CSCs. In this perspective, we will discuss a recent study by Munakata et al., describing a population of colorectal cancer cells with CSC properties, characterized by low proteasome activity and treatment resistance. We will put this finding in a broader view by discussing the challenges and issues inherent with CSC identification, as well as some emerging insights in the CSC concept.