Sgo1 is a potential therapeutic target for hepatocellular carcinoma

被引:24
|
作者
Wang, Lyu-Han [1 ]
Yen, Chia-Jui [3 ]
Li, Tian-Neng [1 ]
Elowe, Sabine [2 ]
Wang, Wen-Ching [1 ]
Wang, Lily Hui-Ching [1 ,4 ]
机构
[1] Natl Tsing Hua Univ, Inst Mol & Cellular Biol, Hsinchu, Taiwan
[2] Univ Laval, Fac Med, Dept Pediat & Reprod Perinatal Hlth & Infant Hlth, CHUL CRCHUQ, Quebec City, PQ G1V 4G2, Canada
[3] Natl Cheng Kung Univ, Inst Clin Med, Tainan 70101, Taiwan
[4] Natl Tsing Hua Univ, Dept Med Sci, Hsinchu, Taiwan
关键词
Shugoshin; Hepatocellular Carcinoma; Hepatitis B Virus; Large Surface Antigen; Mitosis; Catastrophe; Cohesin; ELEVATED ALPHA-FETOPROTEIN; CHROMOSOMAL INSTABILITY; CHROMATID COHESION; ABNORMAL MITOSIS; ALLELIC LOSS; SHUGOSHIN; CANCER; CELLS; CENTROMERE; VARIANT;
D O I
10.18632/oncotarget.2764
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Shugoshin-like protein 1 (Sgo1) is an essential protein in mitosis; it protects sister chromatid cohesion and thereby ensures the fidelity of chromosome separation. We found that the expression of Sgo1 mRNA was relatively low in normal tissues, but was upregulated in 82% of hepatocellular carcinoma (HCC), and correlated with elevated alpha-fetoprotein and early disease onset of HCC. The depletion of Sgo1 reduced cell viability of hepatoma cell lines including HuH7, HepG2, Hep3B, and HepaRG. Using time-lapse microscopy, we showed that hepatoma cells were delayed and ultimately die in mitosis in the absence of Sgo1. In contrast, cell viability and mitotic progression of immortalized cells were not significantly affected. Notably, mitotic cell death induced upon Sgo1 depletion was suppressed upon inhibitions of cyclin-dependent kinase-1 and Aurora kinase-B, or the depletion of mitotic arrest deficient-2. Thus, mitotic cell death induced upon Sgo1 depletion in hepatoma cells is mediated by persistent activation of the spindle assembly checkpoint. Together, these results highlight the essential role of Sgo1 in the maintenance of a proper mitotic progression in hepatoma cells and suggest that Sgo1 is a promising oncotarget for HCC.
引用
收藏
页码:2023 / 2033
页数:11
相关论文
共 50 条
  • [41] TIAM1, a potential synthetic lethal gene and candidate therapeutic target for hepatocellular carcinoma
    Permtermsin, Chalermsin
    Nakjang, Sirinitra
    Ed, Schwalbe
    Reeves, Helen L.
    Strathdee, Gordon
    Shukla, Ruchi
    JOURNAL OF HEPATOLOGY, 2021, 75 : S513 - S513
  • [42] Identification of ROBO1 as a novel hepatocellular carcinoma antigen and a potential therapeutic and diagnostic target
    Ito, Hirotaka
    Funahashi, Shin-ichi
    Yamauchi, Naoko
    Shibahara, Junji
    Midorikawa, Yutaka
    Kawai, Shigeto
    Kinoshita, Yasuko
    Watanabe, Akira
    Hippo, Yoshitaka
    Ohtomo, Toshihiko
    Iwanari, Hiroko
    Nakajima, Atsushi
    Makuuchi, Masatoshi
    Fukayama, Masashi
    Hirata, Yuichi
    Hamakubo, Takao
    Kodama, Tatsuhiko
    Tsuchiya, Masayuki
    Aburatani, Hiroyuki
    CLINICAL CANCER RESEARCH, 2006, 12 (11) : 3257 - 3264
  • [43] PELP1 Is a Novel Therapeutic Target in Hepatocellular Carcinoma
    Nassar, Khaled Mohamed
    Yang, Xue
    Baker, Adriana
    Gopalam, Rahul
    Arnold, William C.
    Adeniran, Timilehin T.
    Hernandez Fernandez, Marian H.
    Mahajan, Megharani
    Lai, Zhao
    Chen, Yidong
    Sareddy, Gangadhara R.
    Viswanadhapalli, Suryavathi
    Sun, Lu-Zhe
    Vadlamudi, Ratna K.
    Pratap, Uday P.
    CANCER RESEARCH COMMUNICATIONS, 2024, 4 (10): : 2610 - 2620
  • [44] Human Sgo1 downregulation leads to chromosomal instability in colorectal cancer
    Iwaizumi, M.
    Shinmura, K.
    Mori, H.
    Yamada, H.
    Suzuki, M.
    Kitayama, Y.
    Igarashi, H.
    Nakamura, T.
    Suzuki, H.
    Watanabe, Y.
    Hishida, A.
    Ikuma, M.
    Sugimura, H.
    GUT, 2009, 58 (02) : 249 - 260
  • [45] Emerging role of silent information regulator 1 (SIRT1) in hepatocellular carcinoma: a potential therapeutic target
    Wu, Yuting
    Meng, Xiaoming
    Huang, Cheng
    Li, Jun
    TUMOR BIOLOGY, 2015, 36 (06) : 4063 - 4074
  • [46] Discovery of NKCC1 as a potential therapeutic target to inhibit hepatocellular carcinoma cell growth and metastasis
    Zhou, Yaya
    Sun, Wei
    Chen, Ning
    Xu, Chen
    Wang, Xinxin
    Dong, Kun
    Zhang, Binxue
    Zhang, Jian
    Hao, Ning
    Sun, Aihua
    Wei, Handong
    He, Fuchu
    Jiang, Ying
    ONCOTARGET, 2017, 8 (39) : 66328 - 66342
  • [47] ASO Author Reflections: SCNM1 as a Novel Driver of Hepatocellular Carcinoma and a Potential Therapeutic Target
    Ofuchi, Takashi
    Otsu, Hajime
    Mimori, Koshi
    ANNALS OF SURGICAL ONCOLOGY, 2025, : 4522 - 4523
  • [48] Ribonuclease 7-driven activation of ROS1 is a potential therapeutic target in hepatocellular carcinoma
    Liu, Chunxiao
    Zha, Zhengyu
    Zhou, Chenhao
    Chen, Yeh
    Xia, Weiya
    Wang, Ying-Nai
    Lee, Heng-Huan
    Yin, Yirui
    Yan, Meisi
    Chang, Chiung-Wen
    Chan, Li-Chuan
    Qiu, Yufan
    Li, Hui
    Li, Chia-Wei
    Hsu, Jung-Mao
    Hsu, Jennifer L.
    Wang, Shao-Chun
    Ren, Ning
    Hung, Mien-Chie
    JOURNAL OF HEPATOLOGY, 2021, 74 (04) : 907 - 918
  • [49] DDR1 is a Novel Biomarker and Potential Therapeutic Target for the Combination Treatment of Liver Hepatocellular Carcinoma
    Li, Tianxing
    Hu, Hao
    Song, Yuhao
    Shi, Yihai
    Hu, Dingtao
    Shen, Weifeng
    Ning, Beifang
    CANCER CONTROL, 2024, 31
  • [50] CtBP1 is involved in epithelial-mesenchymal transition and is a potential therapeutic target for hepatocellular carcinoma
    Zhang, Xiao-Ling
    Huang, Cheng-Xin
    Zhang, Jie
    Inoue, Akira
    Zeng, Si-En
    Xiao, Sheng-Jun
    ONCOLOGY REPORTS, 2013, 30 (02) : 809 - 814