방사선생물학

본문글자크기
  • [Cell Death Dis.] Kinesin Light Chain 4 as a New Target for Lung Cancer Chemoresistance via Targeted Inhibition of Checkpoint Kinases in the DNA Repair Network 항암방사선저항성에서의 표적으로서의 KLC4

    KIRAMS / 백정화, 황상구*

  • 출처
    Cell Death Dis.
  • 등재일
    2020 May 26
  • 저널이슈번호
    11(5):398. doi: 10.1038/s41419-020-2592-z.
  • 내용

    바로가기  >

    Abstract
    The poor therapeutic efficacy of non-small cell lung cancer (NSCLC) is partly attributed to the acquisition of chemoresistance. To investigate the mechanism underlying this resistance, we examined the potential link between kinesin light chain 4 (KLC4), which we have previously reported to be associated with radioresistance in NSCLC, and sensitivity to chemotherapy in human lung cancer cell lines. KLC4 protein levels in lung cancer cells correlated with the degree of chemoresistance to cisplatin treatment. Furthermore, KLC4 silencing enhanced the cytotoxic effect of cisplatin by promoting DNA double-strand breaks and apoptosis. These effects were mediated by interaction with the checkpoint kinase CHK2, as KLC4 knockdown increased CHK2 activation, which was further enhanced in combination with cisplatin treatment. In addition, KLC4 and CHEK2 expression levels showed negative correlation in lung tumor samples from patients, and KLC4 overexpression correlated negatively with survival. Our results indicate a novel link between the KLC4 and CHK2 pathways regulating DNA damage response in chemoresistance, and highlight KLC4 as a candidate for developing lung cancer-specific drugs and customized targeted molecular therapy.

     

    Affiliations

    Jeong-Hwa Baek  1 , Hong Shik Yun  2 , Ju-Young Kim  3   4 , Janet Lee  3 , Yeon-Joo Lee  3 , Chang-Woo Lee  4 , Jie-Young Song  3 , Jiyeon Ahn  3 , Jong Kuk Park  3 , Jae-Sung Kim  3 , Kee-Ho Lee  3 , Eun Ho Kim  5 , Sang-Gu Hwang  6
    1 Radiation Biology Research Team, Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan, 46033, Republic of Korea.
    2 Radiation Oncology Branch, National Cancer Institute, NIH, Bethesda, MD, USA.
    3 Division of Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences, Seoul, 01812, Korea.
    4 Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, 440-746, Korea.
    5 Department of Biochemistry, School of Medicine, Daegu Catholic University, 33, 17-gil, Duryugongwon-ro, Nam-gu, Daegu, Korea. eh140149@cu.ac.kr.
    6 Division of Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences, Seoul, 01812, Korea. sgh63@kcch.re.kr.

  • 편집위원

    NSCLC의 항암저항성은 치료효율저하의 주요 원인으로 작용한다. 본 연구는 신규 항암저항성 표적인자인 KLC4가 checkpoint kinase CHK2와의 interaction을 통해 항암 저항성에 관여함을 규명함으로써, NSCLC의 분자치료를 위한 기반을 제공하였다.

    2020-07-02 15:33:58

  • 덧글달기
    덧글달기
       IP : 44.222.169.53

    등록