例如:"lncRNA", "apoptosis", "WRKY"

Kinesin light chain 4 as a new target for lung cancer chemoresistance via targeted inhibition of checkpoint kinases in the DNA repair network.

Cell Death Dis. 2020 May 26;11(5):398
Jeong-Hwa Baek 1 , Hong Shik Yun 2 , Ju-Young Kim 3 , Janet Lee 4 , Yeon-Joo Lee 4 , Chang-Woo Lee 3 , Jie-Young Song 4 , Jiyeon Ahn 4 , Jong Kuk Park 4 , Jae-Sung Kim 4 , Kee-Ho Lee 4 , Eun Ho Kim 5 , Sang-Gu Hwang 6
Jeong-Hwa Baek 1 , Hong Shik Yun 2 , Ju-Young Kim 3 , Janet Lee 4 , Yeon-Joo Lee 4 , Chang-Woo Lee 3 , Jie-Young Song 4 , Jiyeon Ahn 4 , Jong Kuk Park 4 , Jae-Sung Kim 4 , Kee-Ho Lee 4 , Eun Ho Kim 5 , Sang-Gu Hwang 6
+ et al

[No authors listed]

Author information
  • 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 Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, 440-746, Korea.
  • 4 Division of Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences, Seoul, 01812, 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.

摘要


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.