title: Nanog-induced dedifferentiation of p53-deficient mouse astrocytes into brain cancer stem-like cells.
abstract: Self-renewal, differentiation, and tumorigenicity characterize cancer stem cells (CSCs), which are rare and maintained by specific cell fate regulators. CSCs are isolated from glioblastoma multiforme (GBM) and may be responsible for the lethality of incurable brain tumors. Brain CSCs may arise from the transformation of undifferentiated, nestin-positive neural stem or progenitor cells and GFAP-expressing astrocytes. Here, we report a role of Nanog in the genesis of cancer stem-like cells. Using primary murine p53-knockout astrocytes (p53(-/-) astrocytes), we provide evidence that enforced Nanog expression can increase the cellular growth rate and transform phenotypes in vitro and in vivo. In addition, Nanog drives p53(-/-) astrocytes toward a dedifferentiated, CSC-like phenotype with characteristic neural stem cell/progenitor marker expression, neurosphere formation, self-renewal activity, and tumor development. These findings suggest that Nanog promotes dedifferentiation of p53-deficient mouse astrocytes into cancer stem-like cells by changing the cell fate and transforming cell properties.
authors.affiliation: Laboratory of Cell Function Regulation, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Jai-Hee
authors.initials: JH
authors.lastname: Moon
authors.forename: Suhyun
authors.initials: S
authors.lastname: Kwon
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Jun
authors.forename: Aeree
authors.initials: A
authors.lastname: Kim
authors.forename: Kwang Youn
authors.initials: KY
authors.lastname: Whang
authors.forename: Hyunggee
authors.initials: H
authors.lastname: Kim
authors.forename: Sejong
authors.initials: S
authors.lastname: Oh
authors.forename: Byung Sun
authors.initials: BS
authors.lastname: Yoon
authors.forename: Seungkwon
authors.initials: S
authors.lastname: You
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D054337:Cell Dedifferentiation; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D016159:Tumor Suppressor Protein p53