Radioresistance remains a major obstacle for the radiotherapy treatment of cancer. Previous studies have demonstrated that the radioresistance of cancer is due to the existence of intrinsic cancer stem cells (CSCs), which represent a small, but radioresistant cell subpopulation that exist in heterogeneous tumors. By contrast, non-stem cancer cells are considered to be radiosensitive and thus, easy to kill. However, recent studies have revealed that under conditions of radiation-induced stress, theoretically radiosensitive non-stem cancer cells may undergo dedifferentiation subsequently obtaining the phenotypes and functions of CSCs, including high resistance to radiotherapy, which indicates that radiation may directly result in the generation of novel CSCs from non-stem cancer cells. These findings suggest that in addition to intrinsic CSCs, non-stem cancer cells may also contribute to the relapse and metastasis of cancer following transformation into CSCs. This review aims to investigate the radiation-induced generation of CSCs, its association with epithelial-mesenchymal transition and its significance with regard to the radioresistance of cancer.

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For dendritic cells (DCs) to initiate an immune response, their ability to migrate and to produce interleukin-12 (IL-12) is crucial. It has been previously shown that low-dose radiation (LDR) promoted IL-12 production by DCs, resulting in increased DC activity that contributed to LDR hormesis in the immune system. However, the molecular mechanism of LDR-induced IL-12 production, as well as the effect of LDR on DC migration capacity require further elucidation. Using the JAWSII immortalized mouse dendritic cell line, we showed that in vitro X-ray irradiation (0.2 Gy) of DCs significantly increased DC migration and IL-12 production, and upregulated CCR7. The neutralizing antibody against CCR7 has been shown to abolish LDR-enhanced DC migration, demonstrating that CCR7 mediates LDR-promoting DC migration. We identified nuclear factor kappaB (NF-κB) as the central signaling pathway that mediated LDR-enhanced expression of IL-12 and CCR7 based on findings that 0.2 Gy X-ray irradiation activated NF-κB, showing increased nuclear p65 translocation and NF-κB DNA-binding activity, while an NF-κB inhibitor blocked LDR-enhanced expression of IL-12 and CCR7, as well as DC migration. Finally, we demonstrated that 0.2 Gy X-ray irradiation promoted ATM phosphorylation and reactive oxygen species generation; however, only the ATM inhibitor abolished the LDR-induced NF-κB-mediated expression of IL-12 and CCR7. Altogether, our data show that exposure to LDR resulted in a hormetic effect on DCs regarding CCR7-mediated migration and IL-12 production by activating the ATM/NF-κB pathway.

Polo-like kinase (Plk)1 contributes to the development of human cancer via multiple mechanisms, such as promoting the migration of cancer cells. However, the mechanistic basis for the regulation of cell migration by Plk1 remains unknown. To address this question, the present study investigated the effect of Plk1 inhibition on the migration of human lung adenocarcinoma epithelial A549 cells and the molecular factors involved. A549 cells were treated with the Plk1 inhibitor, BI2536, and cell migration was evaluated with the wound-healing assay. The expression of matrix metallopeptidase (MMP)2, vascular endothelial growth factor (VEGF)A, total and phosphorylated signal transducer and activator of transcription (STAT)3 was assessed by western blotting and reverse transcription-polymerase chain reaction following Plk1 knockdown and/or STAT3 overexpression. The interaction between Plk1 and STAT3 was evaluated by co-immunoprecipitation. The levels of MMP2 and VEGFA were decreased by treatment with Plk1 inhibitor. The phosphorylation of STAT3, which acts upstream of MMP2 and VEGFA, was also decreased by Plk1 knockdown, an effect that was abrogated by STAT3 overexpression. In addition, Plk1 was detected to bind with STAT3 either directly or as part of a complex by co-immunoprecipitation experiments. These results indicated that Plk1 may promote the migration of A549 cells via regulation of STAT3 signaling.

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