Growth factor signaling regulates breast cancer stem cells.

Abstract

Accumulating evidence suggests that cancer stem cells—which make up only a small proportion of heterogeneous tumor cells—possess a greater ability to maintain tumor formation than other tumor cell types. Although the concept of cancer stem cells greatly impacts cancer biology and evokes a reconsideration of cancer treatment, the molecular mechanisms involved in the contribution of cancer stem cells to tumorigenesis remain to be obscure. We found that heregulin (HRG), a ligand for HER3/ErbB3, induced tumor sphere formation of a breast cancer stem cell (BCSC)-enriched population as well as in breast cancer cell lines. HRG-induced tumor sphere formation was reduced by treatment with inhibitors for phosphatidyl inositol 3-kinase (PI3K). Furthermore, we found that the expression of IL8, a regulator of self-renewal in BCSC-enriched populations, was induced by HRG through the activation of the PI3K/NF-κB pathway. These findings illustrate that HRG/ErbB3 signaling appears to maintain tumor sphere formation through a PI3K/NF-κB pathway in human breast cancer.