Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Calcium-binding protein S100P is a new target gene of MACC1, drives colorectal cancer metastasis and serves as a prognostic biomarker

[img]
Preview
PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
2MB
[img] Other (Supplementary Information)
1MB

Item Type:Article
Title:Calcium-binding protein S100P is a new target gene of MACC1, drives colorectal cancer metastasis and serves as a prognostic biomarker
Creators Name:Schmid, F. and Dahlmann, M. and Röhrich, H. and Kobelt, D. and Hoffmann, J. and Burock, S. and Walther, W. and Stein, U.
Abstract:BACKGROUND: The metastasis inducing gene MACC1 is a prognostic and predictive biomarker for metastasis in several cancers. Its mechanism of inducing metastasis includes the transcriptional control of other cancer-related target genes. Here, we investigate the interplay with the metastasis driver S100P in CRC progression. METHODS: MACC1-dependent S100P expression was analysed by qRT-PCR. The binding of MACC1 to the S100P promoter was determined by ChIP. Alterations in cell proliferation and motility were determined by functional in vitro assays. In vivo metastasis after intrasplenic transplantation was assessed by bioluminescence imaging and evaluation of tumour growth and liver metastasis. The prognostic value of S100P was determined in CRC patients by ROC-based Kaplan-Meier analyses. RESULTS: Expression of S100P and MACC1 correlated positively in CRC cells and colorectal tumours. MACC1 was found binding to the S100P promoter and induces its expression. The overexpression of S100P increased proliferation, migration and invasion in vitro and significantly induced liver metastasis in vivo. S100P expression was significantly elevated in metachronously metastasising CRC and was associated with shorter metastasis-free survival. CONCLUSIONS: We identified S100P as a transcriptional target gene of MACC1. Expression of S100P increases the metastatic potential of CRC cells in vitro and in vivo, and serves as a prognostic biomarker for metastasis-free survival of CRC patients, emphasising novel therapeutic interventions targeting S100P.
Keywords:Calcium-Binding Proteins, Colorectal Neoplasms, Neoplastic Gene Expression Regulation, Liver Neoplasms, Neoplasm Proteins, Prognosis, Trans-Activators, Transcription Factors
Source:British Journal of Cancer
ISSN:0007-0920
Publisher:Springer Nature
Volume:127
Number:4
Page Range:675-685
Date:1 September 2022
Official Publication:https://doi.org/10.1038/s41416-022-01833-3
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library