PIK3R3 inhibits cell senescence through p53/p21 signaling

被引:42
作者
Chen, Qianzhi [1 ,2 ]
Sun, Xuling [1 ]
Luo, Xuelai [1 ]
Wang, Jing [3 ]
Hu, Junbo [1 ]
Feng, Yongdong [1 ]
机构
[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept GI,Canc Res Inst, Wuhan, Hubei, Peoples R China
[2] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Breast & Thyroid Surg, Wuhan, Hubei, Peoples R China
[3] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Immunol, Basic Med, Wuhan, Hubei, Peoples R China
基金
中国国家自然科学基金;
关键词
TUMOR-SUPPRESSOR; UP-REGULATION; CANCER; P21; RB;
D O I
10.1038/s41419-020-02921-z
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Cellular senescence is a stress response of human cells that removes potentially harmful cells by initiating cell cycle arrest. Inducing senescence of tumor cells may be an effective tumor-inhibiting strategy. In this study we found that PIK3R3 could inhibit the cell senescence of colorectal cancer cells and promote cell proliferation through the p53/p21 signal pathway. PIK3R3 could bind to p53 and inhibit the binding of p53 to the p21 gene promoter region, and thus affecting the transcriptional activity of p21 gene. Our study has provided new evidence of the role of PIK3R3 in p53 regulation and inhibition of PIK3R3 may be one of the potential targets of tumor therapy.
引用
收藏
页数:12
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共 35 条
[1]   Cell survival and metastasis regulation by Akt signaling in colorectal cancer [J].
Agarwal, Ekta ;
Brattain, Michael G. ;
Chowdhury, Sanjib .
CELLULAR SIGNALLING, 2013, 25 (08) :1711-1719
[2]   Rb, mcl-1 and p53 expression correlate with clinical outcome in patients with liver metastases from colorectal cancer [J].
Backus, HHJ ;
van Riel, JMGH ;
van Groeningen, CJ ;
Vos, W ;
Dukers, DF ;
Bloemena, E ;
Wouters, D ;
Pinedo, HM ;
Peters, GJ .
ANNALS OF ONCOLOGY, 2001, 12 (06) :779-785
[3]   Colorectal cancer [J].
Brenner, Hermann ;
Kloor, Matthias ;
Pox, Christian Peter .
LANCET, 2014, 383 (9927) :1490-1502
[4]   Microbiome, inflammation and colorectal cancer [J].
Chen, Ju ;
Pitmon, Elise ;
Wang, Kepeng .
SEMINARS IN IMMUNOLOGY, 2017, 32 (0C) :43-53
[5]   Poor-prognosis colon cancer is defined by a molecularly distinct subtype and develops from serrated precursor lesions [J].
De Sousa E Melo, Felipe ;
Wang, Xin ;
Jansen, Marnix ;
Fessler, Evelyn ;
Trinh, Anne ;
de Rooij, Laura P. M. H. ;
de Jong, Joan H. ;
de Boer, Onno J. ;
van Leersum, Ronald ;
Bijlsma, Maarten F. ;
Rodermond, Hans ;
van der Heijden, Maartje ;
van Noesel, Carel J. M. ;
Tuynman, Jurriaan B. ;
Dekker, Evelien ;
Markowetz, Florian ;
Medema, Jan Paul ;
Vermeulen, Louis .
NATURE MEDICINE, 2013, 19 (05) :614-618
[6]   p21WAF1/Cip1:: more than a break to the cell cycle? [J].
Dotto, GP .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2000, 1471 (01) :M43-M56
[7]   ALTERED REGULATION OF G(1)-CYCLINS IN SENESCENT HUMAN-DIPLOID FIBROBLASTS - ACCUMULATION OF INACTIVE CYCLIN-E-CDK2 AND CYCLIN-D1-CDK2 COMPLEXES [J].
DULIC, V ;
DRULLINGER, LF ;
LEES, E ;
REED, SI ;
STEIN, GH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (23) :11034-11038
[8]   p21(WAF1) Mediates Cell-Cycle Inhibition, Relevant to Cancer Suppression and Therapy [J].
El-Deiry, Wafik S. .
CANCER RESEARCH, 2016, 76 (18) :5189-5191
[9]   WAF1, A POTENTIAL MEDIATOR OF P53 TUMOR SUPPRESSION [J].
ELDEIRY, WS ;
TOKINO, T ;
VELCULESCU, VE ;
LEVY, DB ;
PARSONS, R ;
TRENT, JM ;
LIN, D ;
MERCER, WE ;
KINZLER, KW ;
VOGELSTEIN, B .
CELL, 1993, 75 (04) :817-825
[10]   Metastatic Colorectal Cancer: Current State and Future Directions [J].
Fakih, Marwan G. .
JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (16) :1809-+