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

被引：77

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

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2019年 / 20卷 / 23期

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

页数：19

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