Anti-metastatic effect of metformin via repression of interleukin 6-induced epithelial- mesenchymal transition in human colon cancer cells

Sanghee Kang, Bo Ram Kim, Myoung Hee Kang, Dae Young Kim, Dae Hee Lee, Sang Cheul Oh, Byung Wook Min, Jun Won Um

Research output: Contribution to journalArticle

Abstract

Metformin, a first-line drug used to treat type 2 diabetes, has also been shown to have anticancer effects against a variety of malignancies, including colorectal cancer. Although inhibition of the mTOR pathway is known to be the most important mechanism for the antitumor effects of metformin, other mechanisms remain unclear. The purpose of this study was to identify the antitumor mechanism of metformin in colorectal cancer using high-throughput data, and then test the mechanism experimentally. We identified the gene signature of metformin- treated colon cancer cells. This signature was processed for prediction using colon adenocarcinoma patient data from the Cancer Genome Atlas to classify the patients showing a gene expression pattern similar to that in metformin-treated cells. This patient group showed better overall and disease-free survival. Furthermore, pathway analysis revealed that the metformin-predicted group was characterized by decreased interleukin (IL)-6 pathway signaling, epithelial-mesenchymal transition, and colon cancer metastatic signaling. We induced epithelial-mesenchymal transition in colon cancer cell lines via IL-6 treatment, which increased cell motility and promoted invasion. However, these effects were blocked by metformin. These findings suggest that blockade of IL-6-induced epithelial-mesenchymal transition is an antitumor mechanism of metformin.

Original languageEnglish
Article numbere0205449
JournalPLoS One
Volume13
Issue number10
DOIs
Publication statusPublished - 2018 Oct 1

Fingerprint

metformin
Epithelial-Mesenchymal Transition
Metformin
colorectal neoplasms
interleukin-6
Colonic Neoplasms
Interleukin-6
Cells
Colorectal Neoplasms
Genes
neoplasm cells
Atlases
Medical problems
adenocarcinoma
cell movement
noninsulin-dependent diabetes mellitus
Gene expression
Type 2 Diabetes Mellitus
Disease-Free Survival
colon

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Anti-metastatic effect of metformin via repression of interleukin 6-induced epithelial- mesenchymal transition in human colon cancer cells. / Kang, Sanghee; Kim, Bo Ram; Kang, Myoung Hee; Kim, Dae Young; Lee, Dae Hee; Oh, Sang Cheul; Min, Byung Wook; Um, Jun Won.

In: PLoS One, Vol. 13, No. 10, e0205449, 01.10.2018.

Research output: Contribution to journalArticle

@article{3151febe5f69470eb443ce616497a990,
title = "Anti-metastatic effect of metformin via repression of interleukin 6-induced epithelial- mesenchymal transition in human colon cancer cells",
abstract = "Metformin, a first-line drug used to treat type 2 diabetes, has also been shown to have anticancer effects against a variety of malignancies, including colorectal cancer. Although inhibition of the mTOR pathway is known to be the most important mechanism for the antitumor effects of metformin, other mechanisms remain unclear. The purpose of this study was to identify the antitumor mechanism of metformin in colorectal cancer using high-throughput data, and then test the mechanism experimentally. We identified the gene signature of metformin- treated colon cancer cells. This signature was processed for prediction using colon adenocarcinoma patient data from the Cancer Genome Atlas to classify the patients showing a gene expression pattern similar to that in metformin-treated cells. This patient group showed better overall and disease-free survival. Furthermore, pathway analysis revealed that the metformin-predicted group was characterized by decreased interleukin (IL)-6 pathway signaling, epithelial-mesenchymal transition, and colon cancer metastatic signaling. We induced epithelial-mesenchymal transition in colon cancer cell lines via IL-6 treatment, which increased cell motility and promoted invasion. However, these effects were blocked by metformin. These findings suggest that blockade of IL-6-induced epithelial-mesenchymal transition is an antitumor mechanism of metformin.",
author = "Sanghee Kang and Kim, {Bo Ram} and Kang, {Myoung Hee} and Kim, {Dae Young} and Lee, {Dae Hee} and Oh, {Sang Cheul} and Min, {Byung Wook} and Um, {Jun Won}",
year = "2018",
month = "10",
day = "1",
doi = "10.1371/journal.pone.0205449",
language = "English",
volume = "13",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "10",

}

TY - JOUR

T1 - Anti-metastatic effect of metformin via repression of interleukin 6-induced epithelial- mesenchymal transition in human colon cancer cells

AU - Kang, Sanghee

AU - Kim, Bo Ram

AU - Kang, Myoung Hee

AU - Kim, Dae Young

AU - Lee, Dae Hee

AU - Oh, Sang Cheul

AU - Min, Byung Wook

AU - Um, Jun Won

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Metformin, a first-line drug used to treat type 2 diabetes, has also been shown to have anticancer effects against a variety of malignancies, including colorectal cancer. Although inhibition of the mTOR pathway is known to be the most important mechanism for the antitumor effects of metformin, other mechanisms remain unclear. The purpose of this study was to identify the antitumor mechanism of metformin in colorectal cancer using high-throughput data, and then test the mechanism experimentally. We identified the gene signature of metformin- treated colon cancer cells. This signature was processed for prediction using colon adenocarcinoma patient data from the Cancer Genome Atlas to classify the patients showing a gene expression pattern similar to that in metformin-treated cells. This patient group showed better overall and disease-free survival. Furthermore, pathway analysis revealed that the metformin-predicted group was characterized by decreased interleukin (IL)-6 pathway signaling, epithelial-mesenchymal transition, and colon cancer metastatic signaling. We induced epithelial-mesenchymal transition in colon cancer cell lines via IL-6 treatment, which increased cell motility and promoted invasion. However, these effects were blocked by metformin. These findings suggest that blockade of IL-6-induced epithelial-mesenchymal transition is an antitumor mechanism of metformin.

AB - Metformin, a first-line drug used to treat type 2 diabetes, has also been shown to have anticancer effects against a variety of malignancies, including colorectal cancer. Although inhibition of the mTOR pathway is known to be the most important mechanism for the antitumor effects of metformin, other mechanisms remain unclear. The purpose of this study was to identify the antitumor mechanism of metformin in colorectal cancer using high-throughput data, and then test the mechanism experimentally. We identified the gene signature of metformin- treated colon cancer cells. This signature was processed for prediction using colon adenocarcinoma patient data from the Cancer Genome Atlas to classify the patients showing a gene expression pattern similar to that in metformin-treated cells. This patient group showed better overall and disease-free survival. Furthermore, pathway analysis revealed that the metformin-predicted group was characterized by decreased interleukin (IL)-6 pathway signaling, epithelial-mesenchymal transition, and colon cancer metastatic signaling. We induced epithelial-mesenchymal transition in colon cancer cell lines via IL-6 treatment, which increased cell motility and promoted invasion. However, these effects were blocked by metformin. These findings suggest that blockade of IL-6-induced epithelial-mesenchymal transition is an antitumor mechanism of metformin.

UR - http://www.scopus.com/inward/record.url?scp=85054770788&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054770788&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0205449

DO - 10.1371/journal.pone.0205449

M3 - Article

VL - 13

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 10

M1 - e0205449

ER -