MedPacto discovers the world's first mechanism of liver metastasis in gastric cancer cells
Nov 03, 2022
LRRFIP2 protein expressed in gastric cancer cells implicates liver metastasis
The results were published in Nature Communications, October issue.
On September 3rd, MedPacto, a genome-based drug discovery and clinical-stage biotechnology company, and its joint research team led by Gillo Research Institute announced that they have discovered the world’s first mechanism of liver metastasis in gastric cancer cells.
The results were published in the October issue of Nature’s sister journal, Nature Communications (IF: 17.694), which is one of the world’s most influential and prestigious outlets for scientific research.
The Research Team revealed the possibility of developing a cancer treatment to suppress liver metastasis by examining the expression level of LRRFIP2 protein and predicting liver metastasis.
In a non-metastatic gastric cancer cell, LRRFIP2 protein binds to CARM1 (coactivator-associated arginine methyltransferase1) protein which is often highly expressed in several cancer types associated with cancer growth and metastasis, leading to the inhibition of the metastatic ability of CARM1 protein.
In metastatic gastric cancer cells, however, the binding ability of LRRFIP2 protein to CARM1 protein is significantly reduced.
The research team found that the LRRFIP2 protein expressed in metastatic gastric cancer cells contains the 7th exon which makes 24 amino acids, unlike the LRRFIP2 protein in non-metastatic cancer cells.
The research team predicted that the insertion of this small exon would result in a structural change in the LRRFIP2 protein while reducing its ability to bind to CARM1.
The team confirmed the marked suppression of liver metastasis in metastatic gastric cancer cells when exon 7 of LRRFIP2 is deleted by the CRISPR/Cas9 system. Of note, patients with high expression of LRRFIP2 protein with exon7 displayed significantly shorter relapse-free survival than those with low expression.
Taken together, these results show that examining the presence of LRRFIP2 with exon7 mRNA in gastric cancer patients may predict liver metastasis. The research team also revealed through a preclinical study that CARM1 inhibitor which is currently undergoing clinical trial has a high therapeutic effect in gastric cancer cells expressing LRRFIP2 with exon7, suggesting the possibility of developing a customized cancer treatment.
“We expect the expression level of an isoform of LRRFIP2 will be an important implication for liver metastasis and the survival period of gastric cancer patients will be predictable.”, stated Seong-jin Kim, head of Gilo Foundation and CEO of MedPacto.