"Liver Metastasis in Gastric Cancer Depends on the Presence of Exon 7 in LRRFIP2 Protein"

Gillo Research Institute and MedPacto Jointly Identify Findings
Published in October Issue of Nature Communications

(Photo by Gillo Research Institute)

[Asia Economy Reporter Chunhee Lee] Domestic researchers have discovered a protein that regulates liver metastasis of gastric cancer cells for the first time in the world.

The Gilo Research Institute, a foundation where Sungjin Kim, CEO of MedPacto, also serves as the head of the research center, announced on the 3rd that through joint research with MedPacto, they identified that the "Leucine-Rich Repeat Flightless-Interacting Protein 2 (LRRFIP2)" plays a decisive role in the metastasis of gastric cancer cells.

The research results were published in the October issue of Nature Communications (IF: 17.694), an online sister journal of Nature.

The research team predicted the presence or absence of liver metastasis in gastric cancer patients based on the expression levels of the LRRFIP2 protein in gastric cancer cells, expecting that this could lead to the development of therapeutics to inhibit liver metastasis in gastric cancer patients in the future.

In non-metastatic gastric cancer cells, the LRRFIP2 protein binds to the "coactivator-associated arginine methyltransferase 1 (CARM1)" protein, which induces cancer growth and metastasis, thereby inhibiting the metastatic ability of CARM1. Conversely, in metastatic gastric cancer cells, the LRRFIP2 protein's binding ability to CARM1 is significantly reduced.

The research team discovered that the LRRFIP2 protein expressed in metastatic gastric cancer cells contains an insertion of the 7th exon, which encodes 24 amino acids, unlike the LRRFIP2 protein in non-metastatic gastric cancer cells. They predicted that this small exon insertion causes structural changes in the LRRFIP2 protein, reducing its binding ability to CARM1.

They confirmed that removing exon 7 of the LRRFIP2 gene in metastatic gastric cancer cells using gene editing significantly suppresses liver metastasis of gastric cancer cells. Additionally, analysis of genetic data from gastric cancer patients showed that patients with high expression of LRRFIP2 protein containing exon 7 had shorter overall survival periods.

With this research, it is expected that investigating the presence of exon 7 messenger RNA (mRNA) of LRRFIP2 in gastric cancer patients will allow prediction of liver metastasis. The research team also demonstrated through animal experiments that CARM1 inhibitors currently undergoing clinical trials have higher therapeutic efficacy in gastric cancer cells expressing LRRFIP2 with exon 7, suggesting the possibility of developing personalized cancer therapies by testing for the presence or absence of exon 7.

Sungjin Kim, head of the Gilo Research Institute, stated, "It is expected that the expression levels of LRRFIP2 isoforms will enable prediction of liver metastasis and survival periods in gastric cancer patients," adding, "This research has laid the foundation for developing new therapeutics to inhibit metastasis in various cancers, including gastric cancer."

This content was produced with the assistance of AI translation services.