Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Inhibition of MACC1-induced metastasis in esophageal and gastric adenocarcinomas

[thumbnail of Original Article]
Preview
PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
2MB
[thumbnail of Supplementary Materials] Other (Supplementary Materials)
121kB

Item Type:Article
Title:Inhibition of MACC1-induced metastasis in esophageal and gastric adenocarcinomas
Creators Name:Treese, C., Werchan, J., von Winterfeld, M., Berg, E., Hummel, M., Timm, L., Rau, B., Daberkow, O., Walther, W., Daum, S., Kobelt, D. and Stein, U.
Abstract:Esophageal and Gastric Adenocarcinomas (AGE/S) are characterized by early metastasis and poor survival. MACC1 (Metastasis Associated in Colon Cancer 1) acts in colon cancer as a metastasis inducer and is linked to reduced survival. This project illuminates the role and potential for the inhibition of MACC1 in AGE/S. Using 266 of 360 TMAs and survival data of AGE/S patients, we confirm the value of MACC1 as an independent negative prognostic marker in AGE/S patients. MACC1 gene expression is correlated with survival and morphological characteristics. In vitro analysis of lentivirally MACC1-manipulated subclones of FLO-1 and OE33 showed enhanced migration induced by MACC1 in both cell line models, which could be inhibited by the MEK1 inhibitor selumetinib. In vivo, the efficacy of selumetinib on tumor growths and metastases of MACC1-overexpressing FLO-1 cells xenografted intrasplenically in NOG mice was tested. Mice with high-MACC1-expressing cells developed faster and larger distant metastases. Treatment with selumetinib led to a significant reduction in metastasis exclusively in the MACC1-positive xenografts. MACC1 is an enhancer of tumor aggressiveness and a predictor of poor survival in AGE/S. This effect can be inhibited by selumetinib.
Keywords:Gastric Cancer, Esophageal Cancer, Metastasis, MACC1, MEK1 Inhibition, Selumetinib, Animals, Mice
Source:Cancers
ISSN:2072-6694
Publisher:MDPI
Volume:14
Number:7
Page Range:1773
Date:31 March 2022
Official Publication:https://doi.org/10.3390/cancers14071773
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library