Hydroxyl-HIF2-alpha is potential therapeutic target for renal cell carcinomas

被引：1
|
作者：
Isono, Takahiro [1 ]
Chano, Tokuhiro [2 ]
Yoshida, Tetsuya [3 ]
Kageyama, Susumu [3 ]
Kawauchi, Akihiro [3 ]
Suzaki, Masafumi [1 ]
Yuasa, Takeshi [4 ]
机构：
[1] Shiga Univ Med Sci, Cent Res Lab, Otsu, Shiga 5202192, Japan
[2] Shiga Univ Med Sci, Dept Clin Lab Med, Otsu, Shiga 5202192, Japan
[3] Shiga Univ Med Sci, Dept Urol, Otsu, Shiga 5202192, Japan
[4] Japanese Fdn Canc Res, Canc Inst Hosp, Dept Urol, Tokyo 1358550, Japan
来源：
AMERICAN JOURNAL OF CANCER RESEARCH | 2016年 / 6卷 / 10期
关键词：
Hypoxia-inducible factors (HIF); hydroxyl-HIF-alpha; HIF2-alpha; renal cell carcinoma (RCC); chetomin; deprivation; Von Hippel-Lindau (VHL); global transcriptome; next generation sequencer (NGS); POU5F1; INTERFERON-ALPHA; DOUBLE-BLIND; INHIBITION; SUFFICIENT; EFFICACY; CANCER; MODEL;
D O I：
暂无
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Dormant cancer cells are deprivation-resistant, and cause a number of problems for therapeutic approaches for cancers. Renal cell carcinomas (RCCs) include deprivation-resistant cells that are resistant to various treatments. In this study, the specific characteristics of deprivation-resistant cells were transcriptionally identified by next generation sequencing. The hypoxia-inducible factors (HIF) transcription factor network was significantly enhanced in deprivation-resistant RCCs compared to the sensitive RCCs. Deprivation-resistant RCCs, that had lost Von Hippel-Lindau tumor suppressor expression, expressed hydroxyl-HIF2-alpha in the nucleus, but not sensitiveRCCs. Hydroxyl-HIF-alpha was also expressed in nuclei of RCC tissue samples. Knockdown for HIF2-alpha, but not HIF1-alpha, induced cell death related to a reduction in HIF-related gene expression in deprivation-resistant RCC cells. Chetomin, a nuclear HIF-inhibitor, induced marked level of cytotoxicity in deprivation-resistant cells, similar to the knockdown of HIF2-alpha. Therefore, hydroxyl-HIF2-alpha might be a potential therapeutic target for RCCs.
引用
收藏
页码：2263 / 2276
页数：14
相关论文
共 50 条
  • [21] Axl receptor tyrosine kinase is a potential therapeutic target in renal cell carcinoma
    H Yu
    R Liu
    B Ma
    X Li
    H-y Yen
    Y Zhou
    V Krasnoperov
    Z Xia
    X Zhang
    A M Bove
    M Buscarini
    D Parekh
    I S Gill
    Q Liao
    M Tretiakova
    D Quinn
    J Zhao
    P S Gill
    British Journal of Cancer, 2015, 113 : 616 - 625
  • [22] FGF19 genetic amplification as a potential therapeutic target in lung squamous cell carcinomas
    Zhang, Xiaochen
    Kong, Mei
    Zhang, Zhen
    Xu, Suzhen
    Yan, Feifei
    Wei, Liyuan
    Zhou, Jianying
    THORACIC CANCER, 2017, 8 (06) : 655 - 665
  • [23] Axl receptor tyrosine kinase is a potential therapeutic target in renal cell carcinoma
    Yu, H.
    Liu, R.
    Ma, B.
    Li, X.
    Yen, H-y
    Zhou, Y.
    Krasnoperov, V.
    Xia, Z.
    Zhang, X.
    Bove, A. M.
    Buscarini, M.
    Parekh, D.
    Gill, I. S.
    Liao, Q.
    Tretiakova, M.
    Quinn, D.
    Zhao, J.
    Gill, P. S.
    BRITISH JOURNAL OF CANCER, 2015, 113 (04) : 616 - 625
  • [24] HIF2α: a new therapeutic target for NAFLD
    Iain Dickson
    Nature Reviews Gastroenterology & Hepatology, 2017, 14 : 691 - 691
  • [25] HIF-2α as a possible therapeutic target of osteoarthritis
    Saito, T.
    Kawaguchi, H.
    OSTEOARTHRITIS AND CARTILAGE, 2010, 18 (12) : 1552 - 1556
  • [26] Targeting HIF2α with an RNAi therapeutic for the treatment of clear cell renal cell carcinoma
    Nicholas, A.
    Wong, S.
    Zhu, R.
    Carlson, J.
    Frankiewicz, A.
    Shu, D.
    Hamilton, H.
    Schienebeck, C.
    Andersen, A.
    Fowler-Watters, M.
    Bertin, S.
    Liu, C.
    Li, X.
    Chen, B.
    Schumacher, J.
    Hegge, J.
    Given, B.
    Li, Z.
    EUROPEAN JOURNAL OF CANCER, 2018, 103 : E9 - E9
  • [27] HIF2α: a new therapeutic target for NAFLD
    Dickson, Iain
    NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2017, 14 (12) : 690 - 690
  • [28] HIF2α-Targeted RNAi Therapeutic Inhibits Clear Cell Renal Cell Carcinoma
    Wong, So C.
    Cheng, Weijun
    Hamilton, Holly
    Nicholas, Anthony L.
    Wakefield, Darren H.
    Almeida, Aaron
    Blokhin, Andrei V.
    Carlson, Jeffrey
    Neal, Zane C.
    Subbotin, Vladimir
    Zhang, Guofeng
    Hegge, Julia
    Bertin, Stephanie
    Trubetskoy, Vladimir S.
    Rozema, David B.
    Lewis, David L.
    Kanner, Steven B.
    MOLECULAR CANCER THERAPEUTICS, 2018, 17 (01) : 140 - 149
  • [29] Targeting HIF-2 α in clear cell renal cell carcinoma: A promising therapeutic strategy
    Martinez-Saez, Olga
    Borau, Pablo Gajate
    Alonso-Gordoa, Teresa
    Molina-Cerrillo, Javier
    Grande, Enrique
    CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2017, 111 : 117 - 123
  • [30] MN/CA IX/G250 as a potential target for immunotherapy of renal cell carcinomas
    Uemura, H
    Nakagawa, Y
    Yoshida, K
    Saga, S
    Yoshikawa, K
    Hirao, Y
    Oosterwijk, E
    BRITISH JOURNAL OF CANCER, 1999, 81 (04) : 741 - 746
12345