Protein Kinase C ¦Á Is a Central Signaling Node and Therapeutic Target for Breast Cancer Stem Cells

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• 作者：Wai?Leong Tam ; Haihui Lu ; Joyce Buikhuisen ; Boon?Seng Soh ; Elgene Lim ; Ferenc Reinhardt ; Zhenhua?Jeremy Wu ; Jordan?A. Krall ; Brian Bierie ; Wenjun Guo ; Xi Chen ; Xiaole?Shirley Liu ; Myles Brown ; Bing Lim ; Robert?A. Weinberg
• 刊名：Cancer Cell
• 出版年：2013
• 出版时间：9 September, 2013
• 年：2013
• 卷：24
• 期：3
• 页码：347-364
• 全文大小：6162 K

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Summary

The epithelial-mesenchymal transition program becomes activated during malignant progression and can enrich for cancer stem cells (CSCs). We report that inhibition of protein kinase C ¦Á (PKC¦Á) specifically targets CSCs but has little effect on non-CSCs. The formation of CSCs from non-stem cells involves a shift from EGFR to PDGFR signaling and results in the PKC¦Á-dependent activation of FRA1. We identified an AP-1 molecular switch in which c-FOS and FRA1 are preferentially utilized in non-CSCs and CSCs, respectively. PKC¦Á and FRA1 expression is associated with the aggressive triple-negative breast cancers, and the depletion of FRA1 results in a mesenchymal-epithelial transition. Hence, identifying molecular features that shift between cell states can be exploited to target signaling components critical to CSCs.