Cancer-associated S100P protein binds and inactivates p53, permits therapy-induced senescence and supports chemoresistance.

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F16%3AN0000022" target="_blank" >RIV/00209805:_____/16:N0000022 - isvavai.cz</a>

Result on the web

<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008377/" target="_blank" >https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008377/</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.18632/oncotarget.7999" target="_blank" >10.18632/oncotarget.7999</a>

Result language

angličtina

Original language name

Cancer-associated S100P protein binds and inactivates p53, permits therapy-induced senescence and supports chemoresistance.

Original language description

S100P belongs to the S100 family of calcium-binding proteins regulativ diverse cellular processes. Certain S100 family members (S100A4 and S100B) are associated with cancer and used as biomarkers of metastatic phenotype. Also S100P is abnormally expressed in tumors and implicated in migration-invasion, survival, and response to therapy. Here we show that S100P binds the tumor suppressor protein p53 as well as its negative regulator HDM2, and that this interaction perturbs the p53-HDM2 binding and increases the p53 level. Paradoxically, the S100P-induced p53 is unable to activate its transcriptional targets hdm2, p21WAF, and bax following the DNA damage. This appears to be related to reduced phosphorylation of serine residues in both N-terminal and C-terminal regions of the p53 molecule. Furthermore, the S100P expression results in lower levels of pro-apoptotic proteins, in reduced cell death response to cytotoxic treatments, followed by stimulation of therapy-induced senescence and increased clonogenic survival. Conversely, the S100P silencing suppresses the ability of cancer cells to survive the DNA damage and form colonies. Thus, we propose that the oncogenic role of S100P involves binding and inactivation of p53, which leads to aberrant DNA damage responses linked with senescence and escape to proliferation. Thereby, the S100P protein may contribute to the outgrowth of aggressive tumor cells resistant to cytotoxic therapy and promote cancer progression.

Czech name

—

Czech description

—

Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

—

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Oncotarget

ISSN

1949-2553

e-ISSN

—

Volume of the periodical

7

Issue of the periodical within the volume

16

Country of publishing house

US - UNITED STATES

Number of pages

15

Pages from-to

22508-22522

UT code for WoS article

000377705900110

EID of the result in the Scopus database

—