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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...

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Autores principales: Sohn, Sung-Hwa, Kim, Bohyun, Sul, Hee Jung, Kim, Yoo Jin, Kim, Hyeong Su, Kim, Hongtae, Seo, Jong Bok, Koh, Youngho, Zang, Dae Young
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
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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.
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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
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