Taspase1 Functions as a Non-Oncogene Addiction Protease that Coordinates Cancer Cell Proliferation and Apoptosis

被引:32
|
作者
Chen, David Y. [1 ]
Liu, Han [1 ]
Takeda, Shugaku [1 ]
Tu, Ho-Chou [1 ]
Sasagawa, Satoru [1 ]
Van Tine, Brian A. [1 ]
Lu, Dongsi [2 ]
Cheng, Emily H-Y. [1 ,2 ]
Hsieh, James J-D. [1 ]
机构
[1] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
关键词
BH3 MIMETIC ABT-737; FAMILY PROTEINS; BCL-2; PROTEINS; MLL FAMILY; MCL-1; BAX; DEGRADATION; ACTIVATION; CLEAVAGE; GENES;
D O I
10.1158/0008-5472.CAN-10-0027
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Taspase1, the mixed lineage leukemia and TFIIA alpha-beta cleaving protease, enables cell proliferation and permits oncogenic initiation. Here, we show its critical role in cancer maintenance and thus offer a new anticancer target. Taspase1 is overexpressed in primary human cancers, and deficiency of Taspase1 in cancer cells not only disrupts proliferation but also enhances apoptosis. Mechanistically, loss of Taspase1 induces the levels of CDK inhibitors (CDKI: p16, p21, and p27) and reduces the level of antiapoptotic MCL-1. Therapeutically, deficiency of Taspase1 synergizes with chemotherapeutic agents and ABT-737, an inhibitor of BCL-2/BCL-X-L, to kill cancer cells. Taspase1 alone or in conjunction with MYC, RAS, or E1A fails to transform NIH/3T3 cells or primary mouse embryonic fibroblasts, respectively, but plays critical roles in cancer initiation and maintenance. Therefore, Taspase1 is better classified as a "non-oncogene addiction" protease, the inhibition of which may offer a novel anticancer therapeutic strategy. The reliance of oncogenes on subordinate non-oncogenes during tumorigenesis underscores the non-oncogene addiction hypothesis in which a large class of non-oncogenes functions to maintain cancer phenotypes and presents attractive anticancer therapeutic targets. The emergence of successful cancer therapeutics targeting non-oncogenes to which cancers are addicted supports the future development and potential application of small-molecule Taspase1 inhibitors for cancer therapy. Cancer Res; 70(13); 5358-67. (C) 2010 AACR.
引用
收藏
页码:5358 / 5367
页数:10
相关论文
共 50 条
  • [21] The Mitochondrial Unfolded Protein Response as a non-Oncogene Addiction to Support Adaptation to Stress during Transformation in Cancer and Beyond
    Kenny, Timothy C.
    Manfredi, Giovanni
    Germain, Doris
    FRONTIERS IN ONCOLOGY, 2017, 7
  • [22] Identification of hyper-rewired genomic stress non-oncogene addiction genes across 15 cancer types
    Jessica Xin Hjaltelin
    Jose M. G. Izarzugaza
    Lars Juhl Jensen
    Francesco Russo
    David Westergaard
    Søren Brunak
    npj Systems Biology and Applications, 5
  • [23] Identification of hyper-rewired genomic stress non-oncogene addiction genes across 15 cancer types
    Hjaltelin, Jessica Xin
    Izarzugaza, Jose M. G.
    Jensen, Lars Juhl
    Russo, Francesco
    Westergaard, David
    Brunak, Soren
    NPJ SYSTEMS BIOLOGY AND APPLICATIONS, 2019, 5
  • [24] Non-Oncogene Addiction of KRAS-Mutant Cancers to IL-1β via Versican and Mononuclear IKKβ
    Spella, Magda
    Ntaliarda, Giannoula
    Skiadas, Georgios
    Lamort, Anne-Sophie
    Vreka, Malamati
    Marazioti, Antonia
    Lilis, Ioannis
    Bouloukou, Eleni
    Giotopoulou, Georgia A. A.
    Pepe, Mario A. A.
    Weiss, Stefanie A. I.
    Petrera, Agnese
    Hauck, Stefanie M. M.
    Koch, Ina
    Lindner, Michael
    Hatz, Rudolph A. A.
    Behr, Juergen
    Arendt, Kristina A. M.
    Giopanou, Ioanna
    Brunn, David
    Savai, Rajkumar
    Jenne, Dieter E. E.
    de Chateau, Maarten
    Yull, Fiona E. E.
    Blackwell, Timothy S. S.
    Stathopoulos, Georgios T. T.
    CANCERS, 2023, 15 (06)
  • [25] An International Cohort of Patients with Small Cell Lung Cancer after a Non-Small Cell Lung Carcinoma Oncogene or Non-Oncogene Addicted
    Levra, Matteo Giaj
    Novello, Silvia
    Ferrer, Leonie
    Barbieri, Fausto
    Mazieres, Julien
    Westeel, Virginie
    Girard, Nicolas
    Poudenx, Michel
    Le Treut, Jacques
    Migliorino, Maria Rita
    Valette, Clarisse Audigier
    Madroszyk, Anne
    Leduc, Charlotte
    Locatelli-Sanchez, Myriam
    Toffart, Anne Claire
    Moro-Sibilot, Denis
    JOURNAL OF THORACIC ONCOLOGY, 2017, 12 (01) : S667 - S667
  • [26] Elucidation of tonic and activated B cell receptor signaling in Burkitt's lymphoma reveals insights into non-oncogene addiction
    Walter, R.
    Corso, J.
    Pan, K. -T
    Doebele, C.
    Yepes, D.
    Sellner, L.
    Tomska, K.
    Bohnenberger, H.
    Zenz, T.
    Urlaub, H.
    Serve, H.
    Oellerich, T.
    ONCOLOGY RESEARCH AND TREATMENT, 2016, 39 : 219 - 219
  • [27] KNTC1 functions as a potential biomarker and oncogene regulating proliferation, migration and apoptosis in gastric cancer
    Qi, Haoran
    Cao, Mengyuan
    Chen, Yanan
    Li, Xiaoya
    Wang, Yingfei
    Dai, Xiaoshuo
    Duan, Xiaoxuan
    Lu, Jing
    INTERNATIONAL IMMUNOPHARMACOLOGY, 2024, 143
  • [28] Future Perspectives in the Second Line Therapeutic Setting for Non-Oncogene Addicted Non-Small-Cell Lung Cancer
    Siringo, Marco
    Baena, Javier
    de Cabo, Helena Bote
    Torres-Jimenez, Javier
    Zurera, Maria
    Zugazagoitia, Jon
    Paz-Ares, Luis
    CANCERS, 2023, 15 (23)
  • [29] Specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 are non-oncogene addiction genes in cancer cells
    Hedrick, Erik
    Cheng, Yating
    Jin, Un-Ho
    Kim, Kyounghyun
    Safe, Stephen
    ONCOTARGET, 2016, 7 (16) : 22245 - 22256
  • [30] Oncogene addiction in non-small cell lung cancer: Focus on ROS1 inhibition
    Facchinetti, Francesco
    Rossi, Giulio
    Bria, Emilio
    Soria, Jean-Charles
    Besse, Benjamin
    Minari, Roberta
    Friboulet, Luc
    Tiseo, Marcello
    CANCER TREATMENT REVIEWS, 2017, 55 : 83 - 95