Findings have been published that elucidate the mechanism by which a key protein promotes the growth of gastric cancer cells. The researchers stated that they demonstrated that inhibiting this protein can markedly reduce cancer cell growth.

A surgical team led by Professor Hee-Seong Kim at Hallym University Sacred Heart Hospital announced on the 2nd that it analyzed the impact of the ‘UCHL1’ protein on gastric cancer cells and published the results in the international journal ‘Pharmaceuticals’. Noting that the ‘ubiquitin-proteasome system (UPS)’, which finely regulates protein synthesis and degradation within cells, is involved in cancer initiation and progression, the team focused its research on UCHL1, a key regulator of this system.

The team collected cancerous tissue and adjacent normal gastric tissue from 48 patients with gastric cancer and conducted comparative analyses. As a result, the UCHL1 protein was found to be expressed at levels more than 70% higher in gastric cancer tissue than in normal tissue. In addition, patients with higher UCHL1 expression had significantly lower overall survival, indicating that UCHL1 is likely a factor directly involved in the progression of gastric cancer.

In experiments using gastric cancer cell lines, the team also found that suppressing UCHL1 expression led to a marked decrease in cancer cell proliferation, migration, and invasion. They additionally confirmed that UCHL1 directly binds to ‘CIP2A’, a key protein that activates growth-promoting signals in cancer cells. The study newly revealed a mechanism whereby UCHL1 promotes cancer cell growth by preventing the degradation of CIP2A.

Based on these analyses, they also identified a clue for suppressing the proliferation of gastric cancer cells. When ‘LDN-57444’, a substance that inhibits UCHL1, was directly applied to gastric cancer cells, cell division was arrested at the first stage of the cell cycle. The researchers stated that these results indicate that pharmacologic inhibition of UCHL1 can produce anticancer effects and suggested that, going forward, therapeutic strategies targeting UCHL1 could be practically applied to the treatment of gastric cancer.

Professor Hee-Seong Kim said, “This study is meaningful in that it systematically clarified that UCHL1 acts as a tumor promoter in gastric cancer and is a protein that regulates cancer cell growth,” adding, “We expect this to lead to the development of therapeutic strategies targeting UCHL1 and to research on prognostic biomarkers.”