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突变型p53在转移进程中的作用

Mutant p53 on the Path to Metastasis.

作者信息

Tang Qiaosi, Su Zhenyi, Gu Wei, Rustgi Anil K

机构信息

Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA.

Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA.

出版信息

Trends Cancer. 2020 Jan;6(1):62-73. doi: 10.1016/j.trecan.2019.11.004. Epub 2019 Dec 16.


DOI:10.1016/j.trecan.2019.11.004
PMID:31952783
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7485681/
Abstract

Metastasis contributes to the vast majority of cancer-related mortality. Regulatory mechanisms of the multistep invasion-metastasis cascade are being unraveled. TP53 is the most frequently mutated gene across human cancers. Accumulating evidence has shown that mutations of TP53 not only lead to loss of function or dominant negative effects, but also promotes a gain of function. Specifically, gain of function mutant p53 promotes cancer cell motility, invasion, and metastasis. Here, we summarize the mechanisms and functions of mutant p53 that foster metastasis in different types of cancers. We also discuss the prognostic value of mutant p53 and current status of therapeutic strategies targeting mutant p53. Future studies will shed light on discovering novel mechanisms of mutant p53-driven cancer metastasis and developing innovative therapeutics to improve clinical outcomes in patients harboring p53 mutations.

摘要

转移是导致绝大多数癌症相关死亡的原因。多步骤侵袭转移级联反应的调控机制正在被逐步阐明。TP53是人类癌症中最常发生突变的基因。越来越多的证据表明,TP53突变不仅会导致功能丧失或显性负效应,还会促进功能获得。具体而言,功能获得性突变型p53会促进癌细胞的运动、侵袭和转移。在此,我们总结了突变型p53在不同类型癌症中促进转移的机制和功能。我们还讨论了突变型p53的预后价值以及针对突变型p53的治疗策略的现状。未来的研究将有助于发现突变型p53驱动癌症转移的新机制,并开发创新疗法以改善携带p53突变患者的临床结局。

相似文献

[1]
Mutant p53 on the Path to Metastasis.

Trends Cancer. 2020-1

[2]
Mutant p53 drives invasion in breast tumors through up-regulation of miR-155.

Oncogene. 2012-7-16

[3]
Tumor-suppressive p53 Signaling Empowers Metastatic Inhibitor KLF17-dependent Transcription to Overcome Tumorigenesis in Non-small Cell Lung Cancer.

J Biol Chem. 2015-8-28

[4]
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Oncogene. 2015-2-26

[5]
p53 Gain-of-Function Mutation Induces Metastasis via BRD4-Dependent CSF-1 Expression.

Cancer Discov. 2023-12-12

[6]
Gain-of-function of mutant p53: mutant p53 enhances cancer progression by inhibiting KLF17 expression in invasive breast carcinoma cells.

Cancer Lett. 2014-11-1

[7]
Inhibition of glucosylceramide synthase eliminates the oncogenic function of p53 R273H mutant in the epithelial-mesenchymal transition and induced pluripotency of colon cancer cells.

Oncotarget. 2016-9-13

[8]
Does TP53 mutation promote ovarian cancer metastasis to omentum by regulating lipid metabolism?

Med Hypotheses. 2013-7-20

[9]
p53-R273H upregulates neuropilin-2 to promote cell mobility and tumor metastasis.

Cell Death Dis. 2017-8-10

[10]
Mutant p53 induces EZH2 expression and promotes epithelial-mesenchymal transition by disrupting p68-Drosha complex assembly and attenuating miR-26a processing.

Oncotarget. 2015-12-29

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本文引用的文献

[1]
COTI-2, A Novel Thiosemicarbazone Derivative, Exhibits Antitumor Activity in HNSCC through p53-dependent and -independent Mechanisms.

Clin Cancer Res. 2019-7-15

[2]
The extracellular matrix in tumor progression and metastasis.

Clin Exp Metastasis. 2019-4-11

[3]
Neoantigen screening identifies broad TP53 mutant immunogenicity in patients with epithelial cancers.

J Clin Invest. 2019-3-1

[4]
TP53 mutations in epithelial ovarian cancer.

Transl Cancer Res. 2016-12

[5]
Mutant p53 as a guardian of the cancer cell.

Cell Death Differ. 2018-12-11

[6]
Mutant p53 in cancer therapy-the barrier or the path.

J Mol Cell Biol. 2019-4-1

[7]
Mutant p53s generate pro-invasive niches by influencing exosome podocalyxin levels.

Nat Commun. 2018-11-29

[8]
New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer.

Nat Rev Mol Cell Biol. 2019-2

[9]
Mutational processes shape the landscape of TP53 mutations in human cancer.

Nat Genet. 2018-9-17

[10]
Every step of the way: integrins in cancer progression and metastasis.

Nat Rev Cancer. 2018-9

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