title: Embryonic stem cell factors and pancreatic cancer.
abstract: 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.
authors.affiliation: Marta Herreros-Villanueva, Daniel D Billadeau, Jin-San Zhang, Division of Oncology Research, Schulze Center for Novel Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, United States.
authors.forename: Marta
authors.initials: M
authors.lastname: Herreros-Villanueva
authors.affiliation: Marta Herreros-Villanueva, Daniel D Billadeau, Jin-San Zhang, Division of Oncology Research, Schulze Center for Novel Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, United States.
authors.forename: Luis
authors.initials: L
authors.lastname: Bujanda
authors.affiliation: Marta Herreros-Villanueva, Daniel D Billadeau, Jin-San Zhang, Division of Oncology Research, Schulze Center for Novel Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, United States.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Billadeau
authors.affiliation: Marta Herreros-Villanueva, Daniel D Billadeau, Jin-San Zhang, Division of Oncology Research, Schulze Center for Novel Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, United States.
authors.forename: Jin-San
authors.initials: JS
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D015195:Drug Design; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D014157:Transcription Factors
keywords: Cancer stem cells; Embryonic stem cells; NANOG; OCT4; Pancreatic cancer; Pluripotency; SOX2