Taiwanese scientists find new pancreatic cancer signaling mechanism

Taipei, Feb. 5 (CNA) Taiwanese researchers from National Chung Cheng University (CCU) and National Cheng Kung University (NCKU) have identified a novel signaling mechanism in pancreatic cancer patients, knowledge of which might help improve survival rates for the deadly disease.

The newly-discovered TIMP1-CD63 signaling mechanism causes KRAS-mutated cells found in around 90 percent of pancreatic cancer patients to evade destruction by the immune system, according to CCU and NCKU press releases on Wednesday.

Moreover, the researchers found that a gene deficiency known as dual specificity phosphatase-2 (DUSP2) is crucial for KRAS-mutated cells to continue growing.

The interaction of these factors results in a "vicious cycle" that promotes the progression of pancreatic cancer, which has a survival rate of less than 10 percent, the researchers said.

"Disruption of the vicious cycle ... may be a highly potential way to inhibit pancreatic cancer progression," the team wrote in their paper, which came following six years of research.

Led by Tsai Shaw-jenq (蔡少正), chair professor at CCU's Department of Physiology, and Shan Yan-shen (沈延盛), dean of NCKU's College of Medicine, the research team published their findings in the leading peer-reviewed scientific journal Molecular Cancer in January 2025.

The paper, titled "Intercellular TIMP-1-CD63 signaling directs the evolution of immune escape and metastasis in KRAS-mutated pancreatic cancer cells," was based on in vitro and in vivo experiments on mice, as well as spatial transcriptomic analysis of tumors.

"Understanding interactions between various cells in pancreatic cancer tumor micro-environments is of great significance for developing blocking strategies, improving early diagnosis rates and improving patient prognoses," Shan said.

The research supports the view that chronic inflammation is a major factor in cancer progression because it draws a large presence of macrophages (large immune system cells that digest pathogens).

The researchers found that this presence triggered the "vicious cycle" of tumor growth based on the interaction of active TIMP-1-CD63 signaling and low DUSP2, revealing that macrophages may actually play a role in "sustaining tumor progression."

The research was primarily funded by Taiwan's National Science and Technology Council and National Health Research Institutes.