title: CHMP4C Disruption Sensitizes the Human Lung Cancer Cells to Irradiation.
abstract: Human lung cancer is highly invasive and the most malignant among human tumors. Adenocarcinoma as a specific type of non-small cell lung cancer occurs with high frequency and is also highly resistant to radiation therapy. Thus, how to avoid radiation resistance and improve radiotherapy effectiveness is a crucial question. In the present study, human lung cancer A549 and H1299 cells were irradiated using γ-rays from a Co60 irradiator. Protein expression was detected by Western blotting. Cell cycle and apoptosis were measured by flow cytometry. Surviving fraction was determined by colony formation assay. γH2AX and 53BP1 foci formation were examined by fluorescence microscopy. In the results, we show that CHMP4C, a subunit of Endosomal sorting complex-III (ESCRT-III), is involved in radiation-induced cellular response. Radiation-induced Aurora B expression enhances CHMP4C phosphorylation in non-small cell lung cancer (NSCLC) cells, maintaining cell cycle check-point and cellular viability as well as resisting apoptosis. CHMP4C depletion enhances cellular sensitivity to radiation, delays S-phase of cell cycle and reduces ionizing radiation (IR)-induced γH2AX foci formation. We found that Aurora B targets CHMP4C and inhibition of Aurora B exhibits similar effects with silencing of CHMP4C in radioresistance. We also confirm that CHMP4C phosphorylation is elevated after IR both in p53-positive and-negative cells, indicating that the close correlation between CHMP4C and Aurora B signaling pathway in mediating radiation resistance is not p53 dependent. Together, our work establishes a new function of CHMP4C in radiation resistance, which will offer a potential strategy for non-small cell lung cancer by disrupting CHMP4C.
authors.affiliation: Key Laboratory of Radiological Protection and Nuclear Emergency, China CDC, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, 2 Xinkang Street, Dewai, Beijing 10088, China. likangtianyi@163.com.
authors.forename: Kang
authors.initials: K
authors.lastname: Li
authors.affiliation: Key Laboratory of Radiological Protection and Nuclear Emergency, China CDC, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, 2 Xinkang Street, Dewai, Beijing 10088, China. jxliu@163.com.
authors.forename: Jianxiang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Radiological Protection and Nuclear Emergency, China CDC, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, 2 Xinkang Street, Dewai, Beijing 10088, China. tianmei1203@aliyun.com.
authors.forename: Mei
authors.initials: M
authors.lastname: Tian
authors.affiliation: Key Laboratory of Radiological Protection and Nuclear Emergency, China CDC, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, 2 Xinkang Street, Dewai, Beijing 10088, China. gaogang@nirp.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Gao
authors.affiliation: Key Laboratory of Radiological Protection and Nuclear Emergency, China CDC, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, 2 Xinkang Street, Dewai, Beijing 10088, China. cedar121@sina.com.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Qi
authors.affiliation: Key Laboratory of Radiological Protection and Nuclear Emergency, China CDC, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, 2 Xinkang Street, Dewai, Beijing 10088, China. ananpy@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Key Laboratory of Radiological Protection and Nuclear Emergency, China CDC, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, 2 Xinkang Street, Dewai, Beijing 10088, China. ruanjl2013@sohu.com.
authors.forename: Jianlei
authors.initials: J
authors.lastname: Ruan
authors.affiliation: Key Laboratory of Radiological Protection and Nuclear Emergency, China CDC, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, 2 Xinkang Street, Dewai, Beijing 10088, China. liuchunxu0214@126.com.
authors.forename: Chunxu
authors.initials: C
authors.lastname: Liu
authors.affiliation: Key Laboratory of Radiological Protection and Nuclear Emergency, China CDC, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, 2 Xinkang Street, Dewai, Beijing 10088, China. suxu@nirp.cn.
authors.forename: Xu
authors.initials: X
authors.lastname: Su
mesh_terms: D017209:Apoptosis; D064107:Aurora Kinase B / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism / Q000528:radiation effects; D005720:Gamma Rays; D006657:Histones / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D011836:Radiation Tolerance; D015290:Second Messenger Systems; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C541008:CHMP4C protein, human; D056827:Endosomal Sorting Complexes Required for Transport; C468783:H2AX protein, human; D006657:Histones; D016159:Tumor Suppressor Protein p53; D064107:Aurora Kinase B
keywords: Aurora B; CHMP4C; human non-small lung cancer cells; radiation