钙结合蛋白 S100P 是 MACC1 的一个新靶基因，驱动结直肠癌转移，可作为预后生物标志物。

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

机构信息

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.

Experimental and Clinical Research Center of the Charité - Universitätsmedizin Berlin and the Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Straße 10, 13125, Berlin, Germany.

出版信息

Br J Cancer. 2022 Sep;127(4):675-685. doi: 10.1038/s41416-022-01833-3. Epub 2022 May 21.

DOI:10.1038/s41416-022-01833-3

PMID:35597866

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9381557/

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.

摘要

背景

转移诱导基因 MACC1 是几种癌症转移的预后和预测生物标志物。其诱导转移的机制包括对其他癌症相关靶基因的转录控制。在这里，我们研究了其与 CRC 进展中的转移驱动基因 S100P 的相互作用。

方法

通过 qRT-PCR 分析 MACC1 依赖性 S100P 表达。通过 ChIP 测定 MACC1 与 S100P 启动子的结合。通过功能体外测定来改变细胞增殖和迁移。通过生物发光成像和肿瘤生长和肝转移的评估来评估脾内移植后的体内转移。通过基于 ROC 的 Kaplan-Meier 分析确定 S100P 在 CRC 患者中的预后价值。