Published online Mar 7, 2014. doi: 10.3748/wjg.v20.i9.2247
Revised: December 15, 2013
Accepted: January 14, 2014
Published online: March 7, 2014
Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic tumor, is a highly aggressive human cancer with the lowest five-year survival rate of any human maligancy primarily due to its early- metastasis and lack of response to chemotherapy and radiation. Recent research suggests that PDAC cells comprise a hierarchy of tumor cells that develop around a population of cancer stem cells (CSCs), a small and distinct population of cancer cells that mediates tumoregenesis, metastasis and resistance to standard treatments. Thus, CSCs could be a target for more effective treatment options. Interestingly, pancreatic CSCs are subject to regulation by some of key embryonic stem cell (ESC) transctiption factors abberently expressed in PDAC, such as SOX2, OCT4 and NANOG. ESC transcription factors are important DNA-binding proteins present in both embryonic and adult somatic cells. The critical role of these factors in reprogramming processes makes them essential not only for embryonic development but also tumorigenesis. Here we provide an overview of stem cell transcription factors, particularly SOX2, OCT4, and NANOG, on their expression and function in pancreatic cancer. In contrast to embryonic stem cells, in which OCT4 and SOX2 are tightly regulated and physically interact to regulate a wide spectrum of target genes, de novo SOX2 expression alone in pancreatic cancer cells is sufficient to promote self-renewal, de-differentiation and imparting stemness characteristics via impacting specific cell cycle regulatory genes and epithelial-mesnechymal transtion driver genes. Thus, targeting ESC factors, particularly SOX2, could be a worthy strategy for pancreatic cancer therapy.
Core tip: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancer due to its early metastasis and lack of response to chemoradiotherapy. Pancreatic cancer stem cells (CSCs) are implicated in tumorigenesis and metastasis as well as therapy resistance, therefore represent a potential target for effective therapeutic options. Recent publications including our own research demonstrate that key embryonic stem cell (ESC) factors, such as OCT4, NANOG and SOX2, are abbrently expressed in PDAC and contribute to pancreatic CSC-like characteristics, such as self-renewal and de-differentiation. This review aims to summarize our current knowledge on the role of ESC factors particulary SOX2 in regulating pancreatic CSC-like feature and implication for therapy.