Cargando…
INC280 inhibits Wnt/β-catenin and EMT signaling pathways and its induce apoptosis in diffuse gastric cancer positive for c-MET amplification
OBJECTIVE: Gastric cancer is more open related to genetic predisposition. In our RNA sequencing study on gastric cancer patients, Runt-related transcription factor-3 (RUNX3) expression was significantly down-regulated in gastric cancer. We showed that decreased levels of RUNX3 are significantly asso...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419497/ https://www.ncbi.nlm.nih.gov/pubmed/30871613 http://dx.doi.org/10.1186/s13104-019-4163-x |
_version_ | 1783403959887593472 |
---|---|
author | Sohn, Sung-Hwa Kim, Bohyun Sul, Hee Jung Kim, Yoo Jin Kim, Hyeong Su Kim, Hongtae Seo, Jong Bok Koh, Youngho Zang, Dae Young |
author_facet | Sohn, Sung-Hwa Kim, Bohyun Sul, Hee Jung Kim, Yoo Jin Kim, Hyeong Su Kim, Hongtae Seo, Jong Bok Koh, Youngho Zang, Dae Young |
author_sort | Sohn, Sung-Hwa |
collection | PubMed |
description | OBJECTIVE: Gastric cancer is more open related to genetic predisposition. In our RNA sequencing study on gastric cancer patients, Runt-related transcription factor-3 (RUNX3) expression was significantly down-regulated in gastric cancer. We showed that decreased levels of RUNX3 are significantly associated with c-MET (r = − 0.4216, P = 0.0130). In addition, c-MET expression is a candidate for targeted therapy in gastric cancer. Therefore, in the present study, the anti-cancer effects of the c-MET inhibitor on gastric cancer cells from positive or negative for c-MET amplification were evaluated. RESULTS: INC280 treatment inhibits growth of a c-MET-amplified MKN45 (RUNX3-positive) and SNU620 (RUNX3-negative) diffuse type cells. Then, INC280 showed the highest inhibition and apoptotic rates with the lowest IC(50)s in MKN45 cells but not in c-MET-reduced MKN28 (intestinal type) cells. We also showed that INC280 inhibits the WNT signaling pathway and SNAIL expression in MKN45 cells. The data indicate that INC280 could be used as therapeutic agents for the prevention or treatment of diffuse gastric cancer positive for c-MET amplification. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-019-4163-x) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6419497 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-64194972019-03-28 INC280 inhibits Wnt/β-catenin and EMT signaling pathways and its induce apoptosis in diffuse gastric cancer positive for c-MET amplification Sohn, Sung-Hwa Kim, Bohyun Sul, Hee Jung Kim, Yoo Jin Kim, Hyeong Su Kim, Hongtae Seo, Jong Bok Koh, Youngho Zang, Dae Young BMC Res Notes Research Note OBJECTIVE: Gastric cancer is more open related to genetic predisposition. In our RNA sequencing study on gastric cancer patients, Runt-related transcription factor-3 (RUNX3) expression was significantly down-regulated in gastric cancer. We showed that decreased levels of RUNX3 are significantly associated with c-MET (r = − 0.4216, P = 0.0130). In addition, c-MET expression is a candidate for targeted therapy in gastric cancer. Therefore, in the present study, the anti-cancer effects of the c-MET inhibitor on gastric cancer cells from positive or negative for c-MET amplification were evaluated. RESULTS: INC280 treatment inhibits growth of a c-MET-amplified MKN45 (RUNX3-positive) and SNU620 (RUNX3-negative) diffuse type cells. Then, INC280 showed the highest inhibition and apoptotic rates with the lowest IC(50)s in MKN45 cells but not in c-MET-reduced MKN28 (intestinal type) cells. We also showed that INC280 inhibits the WNT signaling pathway and SNAIL expression in MKN45 cells. The data indicate that INC280 could be used as therapeutic agents for the prevention or treatment of diffuse gastric cancer positive for c-MET amplification. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-019-4163-x) contains supplementary material, which is available to authorized users. BioMed Central 2019-03-11 /pmc/articles/PMC6419497/ /pubmed/30871613 http://dx.doi.org/10.1186/s13104-019-4163-x Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Note Sohn, Sung-Hwa Kim, Bohyun Sul, Hee Jung Kim, Yoo Jin Kim, Hyeong Su Kim, Hongtae Seo, Jong Bok Koh, Youngho Zang, Dae Young INC280 inhibits Wnt/β-catenin and EMT signaling pathways and its induce apoptosis in diffuse gastric cancer positive for c-MET amplification |
title | INC280 inhibits Wnt/β-catenin and EMT signaling pathways and its induce apoptosis in diffuse gastric cancer positive for c-MET amplification |
title_full | INC280 inhibits Wnt/β-catenin and EMT signaling pathways and its induce apoptosis in diffuse gastric cancer positive for c-MET amplification |
title_fullStr | INC280 inhibits Wnt/β-catenin and EMT signaling pathways and its induce apoptosis in diffuse gastric cancer positive for c-MET amplification |
title_full_unstemmed | INC280 inhibits Wnt/β-catenin and EMT signaling pathways and its induce apoptosis in diffuse gastric cancer positive for c-MET amplification |
title_short | INC280 inhibits Wnt/β-catenin and EMT signaling pathways and its induce apoptosis in diffuse gastric cancer positive for c-MET amplification |
title_sort | inc280 inhibits wnt/β-catenin and emt signaling pathways and its induce apoptosis in diffuse gastric cancer positive for c-met amplification |
topic | Research Note |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419497/ https://www.ncbi.nlm.nih.gov/pubmed/30871613 http://dx.doi.org/10.1186/s13104-019-4163-x |
work_keys_str_mv | AT sohnsunghwa inc280inhibitswntbcateninandemtsignalingpathwaysanditsinduceapoptosisindiffusegastriccancerpositiveforcmetamplification AT kimbohyun inc280inhibitswntbcateninandemtsignalingpathwaysanditsinduceapoptosisindiffusegastriccancerpositiveforcmetamplification AT sulheejung inc280inhibitswntbcateninandemtsignalingpathwaysanditsinduceapoptosisindiffusegastriccancerpositiveforcmetamplification AT kimyoojin inc280inhibitswntbcateninandemtsignalingpathwaysanditsinduceapoptosisindiffusegastriccancerpositiveforcmetamplification AT kimhyeongsu inc280inhibitswntbcateninandemtsignalingpathwaysanditsinduceapoptosisindiffusegastriccancerpositiveforcmetamplification AT kimhongtae inc280inhibitswntbcateninandemtsignalingpathwaysanditsinduceapoptosisindiffusegastriccancerpositiveforcmetamplification AT seojongbok inc280inhibitswntbcateninandemtsignalingpathwaysanditsinduceapoptosisindiffusegastriccancerpositiveforcmetamplification AT kohyoungho inc280inhibitswntbcateninandemtsignalingpathwaysanditsinduceapoptosisindiffusegastriccancerpositiveforcmetamplification AT zangdaeyoung inc280inhibitswntbcateninandemtsignalingpathwaysanditsinduceapoptosisindiffusegastriccancerpositiveforcmetamplification |