Ghisolfi, LauraKeates, AndrewHu, XingwangLee, Dong-kiLi, Chiang2013-03-292012Ghisolfi, Laura, Andrew C. Keates, Xingwang Hu, Dong-ki Lee, and Chiang J. Li. 2012. Ionizing radiation induces stemness in cancer cells. PLoS ONE 7(8): e43628.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:10474253The 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.en-USBiologyDevelopmental BiologyStem CellsMolecular Cell BiologyCellular TypesMedicineOncologyCancer TreatmentRadiation TherapyCancers and NeoplasmsGastrointestinal TumorsHepatocellular CarcinomaBasic Cancer ResearchRadiotherapyJournal Article2013-03-2910.1371/journal.pone.0043628