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Updated: Aug 15, 2026
Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
Targeting Id1 and Id3 inhibits peritoneal metastasis of gastric cancer
Takeshi Tsuchiya1, Yurai Okaji, Nelson H Tsuno
1Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Bunkyo-ku, Japan. tk-tsuchiya@muh.biglobe.ne.jp
Abstract:
Inhibitor of DNA binding (Id) proteins are essential for cell differentiation, proliferation, migration, invasion and angiogenesis. Recently, they have been shown to correlate with less differentiated phenotypes, high malignant potential and poor clinical outcome in various kinds of tumors. In an attempt to develop new strategies for the treatment of peritoneal metastasis of gastric cancer, we prepared an Id1, 3 double-knockdown gastric cancer cell line, MKN45, by RNA interference and investigated its effects on the development of metastatic nodules in the peritoneal cavity. Both cell proliferation and migration capabilities were decreased in Id1, 3 double-knockdown cells, as was their ability to bind to laminin, which could be explained by the decreased expression of integrin alpha6. These are important steps in the metastatic process. In a mouse model, the number of peritoneal metastatic nodules formed by Id1, 3 double-knockdown cells was reduced compared to mock-transfected control cells, as was the size of individual tumors. In this study, we clearly demonstrated that Id1, 3 double-knockdown significantly impaired the ability of gastric cancer cells to form peritoneal metastasis. Id should be considered an ideal target for the treatment and prevention of gastric cancer, and RNA interference is an attractive and promising strategy to achieve it.
Insights
Inhibitors of DNA binding (Id) proteins are crucial in cancer. Targeting Id1 and Id3 with RNA interference significantly reduced gastric cancer peritoneal metastasis in mice by inhibiting cell proliferation and migration.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metastasis
Background:
- Inhibitors of DNA binding (Id) proteins regulate critical cellular processes like differentiation and migration.
- Id proteins are linked to aggressive tumor phenotypes and poor clinical outcomes in various cancers.
- Peritoneal metastasis is a significant challenge in gastric cancer treatment.
Purpose of the Study:
- To investigate the role of Id1 and Id3 in gastric cancer peritoneal metastasis.
- To evaluate the therapeutic potential of targeting Id1 and Id3 using RNA interference.
- To develop novel strategies for treating peritoneal metastasis of gastric cancer.
Main Methods:
- Generated an Id1, 3 double-knockdown MKN45 gastric cancer cell line using RNA interference.
- Assessed cell proliferation, migration, and laminin binding capabilities.
- Utilized a mouse model to evaluate the formation of peritoneal metastatic nodules.
Main Results:
- Id1, 3 double-knockdown cells exhibited reduced proliferation and migration.
- Decreased expression of integrin alpha6 was observed in knockdown cells, affecting laminin binding.
- The number and size of peritoneal metastatic nodules were significantly reduced in mice treated with Id1, 3 double-knockdown cells.
Conclusions:
- Id1, 3 double-knockdown significantly impairs gastric cancer cell ability to form peritoneal metastasis.
- Id proteins represent a promising therapeutic target for gastric cancer peritoneal metastasis.
- RNA interference is a viable strategy for targeting Id proteins in cancer treatment.
