http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Suji Han,Hyemi Shin,Jin-Ku Lee,Zhaoqi Liu,Raul Rabadan,Jeongwu Lee,Jihye Shin,Cheolju Lee,Heekyoung Yang,Donggeon Kim,Sung Heon Kim,Jooyeon Kim,Jeong-Woo Oh,Doo-Sik Kong,Jung-Il Le,Ho Jun Seol,Jung Wo 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-
Glioblastoma (GBM) is the most lethal primary brain tumor with few treatment options. The survival of gliomainitiating cells (GICs) is one of the major factors contributing to treatment failure. GICs frequently produce and respond to their own growth factors that support cell proliferation and survival. In this study, we aimed to identify critical autocrine factors mediating GIC survival and to evaluate the anti-GBM effect of antagonizing these factors. Proteomic analysis was performed using conditioned media from two different patient-derived GBM tumor spheres under a growth factor-depleted status. Then, the antitumor effects of inhibiting an identified autocrine factor were evaluated by bioinformatic analysis and molecular validation. Proteins secreted by sphere-forming GICs promote cell proliferation/survival and detoxify reactive oxygen species (ROS). Among these proteins, we focused on midkine (MDK) as a clinically significant and pathologically relevant autocrine factor. Antagonizing MDK reduced the survival of GBM tumor spheres through the promotion of cell cycle arrest and the consequent apoptotic cell death caused by oxidative stress-induced DNA damage. We also identified PCBP4, a novel molecular predictor of resistance to anti-MDK treatment. Collectively, our results indicate that MDK inhibition is an important therapeutic option by suppressing GIC survival through the induction of ROS-mediated cell cycle arrest and apoptosis.
Han Suji,Shin Hyemi,Lee Jin-Ku,Liu Zhaoqi,Rabadan Raul,Lee Jeongwu,Shin Jihye,Lee Cheolju,Yang Heekyoung,Kim Donggeon,Kim Sung Heon,Kim Jooyeon,Oh Jeong-Woo,Kong Doo-Sik,Lee Jung-Il,Seol Ho Jun,Choi J 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-
An amendment to this paper has been published and can be accessed via a link at the top of the paper.