title: Tumorigenic potential is restored during differentiation in fusion-reprogrammed cancer cells.
abstract: Detailed understanding of the mechanistic steps underlying tumor initiation and malignant progression is critical for insights of potentially novel therapeutic modalities. Cellular reprogramming is an approach of particular interest because it can provide a means to reset the differentiation state of the cancer cells and to revert these cells to a state of non-malignancy. Here, we investigated the relationship between cellular differentiation and malignant progression by the fusion of four independent mouse cancer cell lines from different tissues, each with differing developmental potentials, to pluripotent mouse embryonic stem (ES) cells. Fusion was accompanied by loss of differentiated properties of the four parental cancer cell lines and concomitant emergence of pluripotency, demonstrating the feasibility to reprogram the malignant and differentiative properties of cancer cells. However, the original malignant and differentiative phenotypes re-emerge upon withdrawal of the fused cells from the embryonic environment in which they were maintained. cDNA array analysis of the malignant hepatoma progression implicated a role for Foxa1, and silencing Foxa1 prevented the re-emergence of malignant and differentiation-associated gene expression. Our findings support the hypothesis that tumor progression results from deregulation of stem cells, and our approach provides a strategy to analyze possible mechanisms in the cancer initiation.
authors.affiliation: Department of Cell Biology, Center for Stem Cells and Medicine, Second Military Medical University, Shanghai 200433, People's Republic of China.|Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xian 710061, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Yao
authors.affiliation: Key Laboratory of Molecular and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, People's Republic of China.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xian 710061, People's Republic of China.|Basic Medical College, Shanxi University of Traditional Chinese Medicine, Shanxi 030024, People's Republic of China.
authors.forename: L
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xian 710061, People's Republic of China.
authors.forename: B
authors.initials: B
authors.lastname: Guo
authors.affiliation: Key Laboratory of Molecular and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Hu
authors.affiliation: Key Laboratory of National Education Ministry for Mammalian Reproductive Biology and Biotechnology, Inner Mongolia University, Huhhot 010021, People's Republic of China.
authors.forename: U
authors.initials: U
authors.lastname: Borjigin
authors.affiliation: Key Laboratory of National Education Ministry for Mammalian Reproductive Biology and Biotechnology, Inner Mongolia University, Huhhot 010021, People's Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Pearl Laboratory Animal Science and Technology Co. Ltd, Guangzhou, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Pearl Laboratory Animal Science and Technology Co. Ltd, Guangzhou, People's Republic of China.
authors.forename: M
authors.initials: M
authors.lastname: Lv
authors.affiliation: Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: J T Y
authors.initials: JT
authors.lastname: Lau
authors.affiliation: Key Laboratory of Molecular and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, People's Republic of China.|Key Laboratory of National Education Ministry for Mammalian Reproductive Biology and Biotechnology, Inner Mongolia University, Huhhot 010021, People's Republic of China.|Hepatoscience Inc., Sunnyvale, CA, USA.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of National Education Ministry for Mammalian Reproductive Biology and Biotechnology, Inner Mongolia University, Huhhot 010021, People's Republic of China.
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Cell Biology, Center for Stem Cells and Medicine, Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Y-P
authors.initials: YP
authors.lastname: Hu
mesh_terms: D000328:Adult; D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D002459:Cell Fusion; D045744:Cell Line, Tumor; D065150:Cellular Reprogramming; D018450:Disease Progression; D053595:Embryonic Stem Cells / Q000166:cytology; D006801:Humans; D008822:Mice, Transgenic; D010641:Phenotype; D039904:Pluripotent Stem Cells / Q000166:cytology; D015203:Reproducibility of Results; D013724:Teratoma / Q000473:pathology; D059467:Transcriptome / Q000235:genetics