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Published on: February 22, 2020
Claudin 1 mediates tumor necrosis factor alpha-induced cell migration in human gastric cancer cells
Atsushi Shiozaki1, Hiroki Shimizu1, Daisuke Ichikawa1
1Atsushi Shiozaki, Hiroki Shimizu, Daisuke Ichikawa, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Daisuke Iitaka, Shingo Nakashima, Yoshito Nako, Eigo Otsuji, Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Aim:
To investigate the role of claudin 1 in the regulation of genes involved in cell migration and tumor necrosis factor alpha (TNF-α)-induced gene expression in human gastric adenocarcinoma cells.
Methods:
Knockdown experiments were conducted with claudin 1 small interfering RNA (siRNA), and the effects on the cell cycle, apoptosis, migration and invasion were analyzed in human gastric adenocarcinoma MKN28 cells. The gene expression profiles of cells were analyzed by microarray and bioinformatics.
Results:
The knockdown of claudin 1 significantly inhibited cell proliferation, migration and invasion, and increased apoptosis. Microarray analysis identified 245 genes whose expression levels were altered by the knockdown of claudin 1. Pathway analysis showed that the top-ranked molecular and cellular function was the cellular movement related pathway, which involved MMP7, TNF-SF10, TGFBR1, and CCL2. Furthermore, TNF- and nuclear frctor-κB were the top-ranked upstream regulators related to claudin 1. TNF-α treatment increased claudin 1 expression and cell migration in MKN28 cells. Microarray analysis indicated that the depletion of claudin 1 inhibited 80% of the TNF-α-induced mRNA expression changes. Further, TNF-α did not enhance cell migration in the claudin 1 siRNA transfected cells.
Conclusion:
These results suggest that claudin 1 is an important messenger that regulates TNF-α-induced gene expression and migration in gastric cancer cells. A deeper understanding of these cellular processes may be helpful in establishing new therapeutic strategies for gastric cancer.
Insights
Claudin 1 knockdown inhibits gastric cancer cell migration and invasion. It also significantly impacts tumor necrosis factor alpha (TNF-α)-induced gene expression, suggesting claudin 1 is a key regulator in gastric cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Gastric adenocarcinoma is a significant global health concern.
- Cell migration and invasion are critical processes in cancer metastasis.
- Tumor necrosis factor alpha (TNF-α) plays a complex role in cancer development.
Purpose of the Study:
- To investigate the role of claudin 1 in regulating genes involved in cell migration.
- To determine claudin 1's function in TNF-α-induced gene expression in gastric cancer cells.
Main Methods:
- Claudin 1 was knocked down using small interfering RNA (siRNA) in MKN28 gastric adenocarcinoma cells.
- Cell proliferation, apoptosis, migration, and invasion were analyzed.
- Gene expression profiles were assessed using microarray and bioinformatics.
Main Results:
- Claudin 1 knockdown significantly reduced cell proliferation, migration, and invasion, while increasing apoptosis.
- Microarray analysis revealed 245 genes affected by claudin 1 knockdown, with cellular movement pathways being prominent.
- Claudin 1 depletion inhibited 80% of TNF-α-induced mRNA expression changes and blocked TNF-α-enhanced cell migration.
Conclusions:
- Claudin 1 acts as a crucial mediator in TNF-α-induced gene expression and cell migration in gastric cancer.
- Understanding these mechanisms could lead to novel therapeutic strategies for gastric cancer.
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