Targeting the Oncogenic p53 Mutants in Colorectal Cancer and Other Solid Tumors

被引:72
|
作者
Li, Hui [1 ,2 ,3 ]
Zhang, Jinglin [1 ,2 ,3 ]
Tong, Joanna Hung Man [1 ,3 ]
Chan, Anthony Wing Hung [1 ,3 ]
Yu, Jun [2 ,4 ]
Kang, Wei [1 ,2 ,3 ]
To, Ka Fai [1 ,2 ,3 ]
机构
[1] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Anat & Cellular Pathol, State Key Lab Translat Oncol, Hong Kong, Peoples R China
[2] Chinese Univ Hong Kong, Inst Digest Dis, State Key Lab Digest Dis, Hong Kong, Peoples R China
[3] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Sir YK Pao Canc Ctr, Hong Kong, Peoples R China
[4] Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Peoples R China
关键词
TP53; p53; mutants; colorectal cancer; solid tumor; GAIN-OF-FUNCTION; POLYPOSIS-COLI GENE; ADENOMATOUS POLYPOSIS; UP-REGULATION; THERAPEUTIC APPROACH; SUPPRESSOR FUNCTION; SOMATIC MUTATION; GLIOMA-CELLS; PROMOTES; PROTEIN;
D O I
10.3390/ijms20235999
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Colorectal cancer (CRC) is a kind of solid tumor and the third most common cancer type in the world. It is a heterogeneous disease characterized by genetic and epigenetic aberrations. The TP53 mutation is the key step driving the transition from adenoma to adenocarcinoma. The functional roles of TP53 mutation in tumor development have been comprehensively investigated. In CRC, TP53 mutation was associated with poor prognosis and chemoresistance. A gain of function (GOF) of p53 mutants promotes cell proliferation, migration and invasion through multiple mechanisms. Restoring wild type p53 function, depleting p53 mutants, or intervention by targeting the oncogenic downstreams provides potential therapeutic strategies. In this review, we comprehensively summarize the GOF of p53 mutants in CRC progression as well as in some other solid tumors, and discuss the current strategies targeting p53 mutants in malignancies.
引用
收藏
页数:19
相关论文
共 50 条
  • [41] Different hotspot p53 mutants exert distinct phenotypes and predict outcome of colorectal cancer patients
    Hassin, Ori
    Nataraj, Nishanth Belugali
    Shreberk-Shaked, Michal
    Aylon, Yael
    Yaeger, Rona
    Fontemaggi, Giulia
    Mukherjee, Saptaparna
    Maddalena, Martino
    Avioz, Adi
    Iancu, Ortal
    Mallel, Giuseppe
    Gershoni, Anat
    Grosheva, Inna
    Feldmesser, Ester
    Ben-Dor, Shifra
    Golani, Ofra
    Hendel, Ayal
    Blandino, Giovanni
    Kelsen, David
    Yarden, Yosef
    Oren, Moshe
    NATURE COMMUNICATIONS, 2022, 13 (01)
  • [42] Different hotspot p53 mutants exert distinct phenotypes and predict outcome of colorectal cancer patients
    Ori Hassin
    Nishanth Belugali Nataraj
    Michal Shreberk-Shaked
    Yael Aylon
    Rona Yaeger
    Giulia Fontemaggi
    Saptaparna Mukherjee
    Martino Maddalena
    Adi Avioz
    Ortal Iancu
    Giuseppe Mallel
    Anat Gershoni
    Inna Grosheva
    Ester Feldmesser
    Shifra Ben-Dor
    Ofra Golani
    Ayal Hendel
    Giovanni Blandino
    David Kelsen
    Yosef Yarden
    Moshe Oren
    Nature Communications, 13
  • [43] Tumor suppressor p53 and its mutants in cancer metabolism
    Liu, Juan
    Zhang, Cen
    Hu, Wenwei
    Feng, Zhaohui
    CANCER LETTERS, 2015, 356 (02) : 197 - 203
  • [44] PRIMA-1Met suppresses colorectal cancer independent of p53 by targeting MEK
    Lu, Tao
    Zou, Yanmei
    Xu, Guogang
    Potter, Jane A.
    Taylor, Garry L.
    Duan, Qiuhong
    Yang, Qin
    Xiong, Huihua
    Qiu, Hong
    Ye, Dawei
    Zhang, Peng
    Yu, Shiying
    Yuan, Xianglin
    Zhu, Feng
    Wang, Yihua
    Xiong, Hua
    ONCOTARGET, 2016, 7 (50) : 83017 - 83030
  • [45] Targeting mutant p53 for efficient cancer therapy
    Bykov, Vladimir J. N.
    Eriksson, Sofi E.
    Bianchi, Julie
    Wiman, Klas G.
    NATURE REVIEWS CANCER, 2018, 18 (02) : 89 - 102
  • [46] Targeting mutant p53 in cancer: the latest insights
    Di Agostino, Silvia
    Fontemaggi, Giulia
    Strano, Sabrina
    Blandino, Giovanni
    D'Orazi, Gabriella
    JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2019, 38 (1)
  • [47] A small molecule corrector for p53 mutants found in cancer
    Fallatah, Maryam Mohammed J.
    Demir, Ozlem
    Amaro, Rommie
    Kaiser, Peter
    CANCER RESEARCH, 2023, 83 (07)
  • [48] Targeting mutant p53 stabilization for cancer therapy
    Wang, Jiajian
    Liu, Wenjun
    Zhang, Lanqing
    Zhang, Jihong
    FRONTIERS IN PHARMACOLOGY, 2023, 14
  • [49] Targeting mutant p53 for efficient cancer therapy
    Vladimir J. N. Bykov
    Sofi E. Eriksson
    Julie Bianchi
    Klas G. Wiman
    Nature Reviews Cancer, 2018, 18 : 89 - 102
  • [50] Comprehensive omics studies of p53 mutants in human cancer
    Malhotra, Lakshay
    Singh, Alankrita
    Kaur, Punit
    Ethayathulla, Abdul S.
    BRIEFINGS IN FUNCTIONAL GENOMICS, 2023, 22 (02) : 97 - 108