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 language | English |
|---|---|
| Article number | e0205449 |
| Journal | PLoS One |
| Volume | 13 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2018 Oct 1 |
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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 journal › Article
}
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
C2 - 30308035
AN - SCOPUS:85054770788
VL - 13
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 10
M1 - e0205449
ER -