Ionizing Radiation Induces Stemness in Cancer Cells

被引:161
作者
Ghisolfi, Laura [1 ]
Keates, Andrew C. [1 ]
Hu, Xingwang [1 ]
Lee, Dong-ki [2 ]
Li, Chiang J. [1 ]
机构
[1] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Skip Ackerman Ctr Mol Therapeut,Div Gastroenterol, Boston, MA 02215 USA
[2] Sungkyunkwan Univ, Dept Chem, Global Res Lab RNAi Med, Suwon, South Korea
关键词
TUMOR-INITIATING CELLS; INDUCED GENOMIC INSTABILITY; ACUTE MYELOID-LEUKEMIA; SIDE-POPULATION; SELF-RENEWAL; MULTIDRUG-RESISTANCE; MELANOMA-CELLS; DIFFERENTIATION; GROWTH; CARCINOGENESIS;
D O I
10.1371/journal.pone.0043628
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
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.
引用
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页数:11
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