title: Ionizing radiation induces stemness in cancer cells.
abstract: The cancer stem cell (CSC) model posits the presence of a small number of CSCs in the heterogeneous cancer cell population that are ultimately responsible for tumor initiation, as well as cancer recurrence and metastasis. CSCs have been isolated from a variety of human cancers and are able to generate a hierarchical and heterogeneous cancer cell population. CSCs are also resistant to conventional chemo- and radio-therapies. Here we report that ionizing radiation can induce stem cell-like properties in heterogeneous cancer cells. Exposure of non-stem cancer cells to ionizing radiation enhanced spherogenesis, and this was accompanied by upregulation of the pluripotency genes Sox2 and Oct3/4. Knockdown of Sox2 or Oct3/4 inhibited radiation-induced spherogenesis and increased cellular sensitivity to radiation. These data demonstrate that ionizing radiation can activate stemness pathways in heterogeneous cancer cells, resulting in the enrichment of a CSC subpopulation with higher resistance to radiotherapy.
authors.affiliation: Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Laura
authors.initials: L
authors.lastname: Ghisolfi
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Keates
authors.forename: Xingwang
authors.initials: X
authors.lastname: Hu
authors.forename: Dong-ki
authors.initials: DK
authors.lastname: Lee
authors.forename: Chiang J
authors.initials: CJ
authors.lastname: Li
mesh_terms: D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000528:radiation effects*; D050814:Octamer Transcription Factor-3 / Q000172:deficiency / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000172:deficiency / Q000235:genetics
chemical_list: D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D012333:RNA, Messenger; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors