Why Cancer Risk Persists After Bacteria Are Eliminated: Chinese Researchers Identify a ‘Memory’ Protein

Researchers have uncovered why the risk of gastric cancer does not disappear even after Helicobacter pylori is eliminated. A Chinese research team found that a specific protein leaves cells with a “cancer-causing memory.”

According to BioOn on the 26th (local time), a research team led by Professor Ding Shigang of Peking University Third Hospital published the findings in the international journal Advanced Science.

The team determined that insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) remains active for a long time after Helicobacter pylori infection and drives the development of gastric cancer.

Helicobacter pylori is considered a major risk factor for gastric cancer. However, it has remained unclear how gastric mucosal cells can become cancerous over the long term after a transient infection or after the bacteria are eliminated.

Analyzing gastric epithelial cells, mouse models and human gastric tissue, the team found that Helicobacter pylori infection increases IGF2BP1 expression. High IGF2BP1 expression persisted even after the bacteria were eliminated.

The team explained that the bacteria can induce malignant reprogramming of epithelial cells with only a one-time stimulus.

Persistently elevated IGF2BP1 suppressed oxidative stress and ferroptosis, an iron-dependent form of cell death, helping cancer cells survive and proliferate.

Specifically, IGF2BP1 acted as an N6-methyladenosine (m6A) reader protein to stabilize SLC7A11 mRNA. SLC7A11 is a key molecule that regulates cystine uptake and maintains the cell’s redox balance.

The team reported that inhibiting IGF2BP1 with BTYNB and cucurbitacin B (CuB) reduced tumor growth in cell and xenograft tumor models and also lowered cell viability in patient-derived gastric cancer organoids.

The team said IGF2BP1 is a key mediator linking Helicobacter pylori infection to persistent cancer-causing reprogramming and could be a therapeutic target for Helicobacter pylori-associated gastric cancer.