title: Direct reprogramming of stem cell properties in colon cancer cells by CD44.
abstract: Cancer progression is commonly segregated into processes of primary tumour growth and secondary metastasis. Recent evidence suggests that a subpopulation of cancer cells, cancer stem cells (CSCs), is responsible for tumour growth in cancer. However, the role of CSCs in cancer metastasis is unclear. In this study, we found that the C terminus of CD44 contributes to sphere formation and survival in vitro via the CD44-SRC-integrin axis. In addition, nuclear CD44/acetylated-STAT3 is required for clonal formation in vitro and tumourigenicity in vivo. Nuclear CD44 binds to various promoters identified by chromatin immunoprecipitation-seq, including that of c-myc and Twist1, leading to cell fate change through transcriptional reprogramming. We propose that nuclear CD44/acetylated-STAT3 performs an unexpected tumour-progressing function by enhancing cell outgrowth into structures where cells with properties of CSCs can be generated from differentiated somatic cells in suspension culture, and then exhibit attributes of cells that have undergone an epithelial-mesenchymal transition, leading to tumour metastasis, and a resulting worse prognosis.
authors.affiliation: Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
authors.forename: Ying-Jhen
authors.initials: YJ
authors.lastname: Su
authors.forename: Hsin-Mei
authors.initials: HM
authors.lastname: Lai
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Chang
authors.forename: Guan-Ying
authors.initials: GY
authors.lastname: Chen
authors.forename: Jia-Lin
authors.initials: JL
authors.lastname: Lee
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D003110:Colonic Neoplasms / Q000473:pathology*; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D004247:DNA; D019061:src-Family Kinases