p-21 activated kinase 4 (PAK4) role in pancreatic cancer stem cells

On January 28, 2016 Cancer Letters published an article entitle “p-21 activated kinase 4 (PAK4) maintains stem cell-like phenotypes in pancreatic cancer cells through activation of STAT3 signaling”, which demonstrates that PAK4 regulates pancreatic cancer stemness through STAT3 activation. Particularly expressed in a subpopulation of cancer stem cells (CSCs) co-expressing CD24, CD44 and EpCAM, PAK4 is associated with enhanced levels of transcription factors inducing pluripotency, self-renewal and dedifferentiation properties such as OCT-4/NANOG/SOX2 and KLF-4. Additionally, PAK4 could be inducing resistance to gemcitabine treatment in this subpopulation of cells. Although previous studies observed an association between PAK4 and pancreatic cancer or PAK4 and CSCs, the data here presented are novel demonstrating first experimental evidence of PAK4 in pancreatic cancer stemness. However, experimental strategy is still very limited as conclusion has been drawn by using exclusively two different in vitro cell lines. Importantly, a broader in vitro testing and further clinical approach is required before clinical utility as novel therapeutic target can be claimed.