ARHI as a key regulator of EMT and metastasis in pancreatic cancer via the Notch-1 pathway

  • Hum Genet. 2026 Jun 14;145(1):51. doi: 10.1007/s00439-026-02845-2.
Jingjing Liu  #  1  2 ,  Yiqun Zhao  #  3 ,  Ying Wang  #  4 ,  Ying Shi  5 ,  Qiang Zhi  3 ,  Linlin Chen  3 ,  Yuhao Ke  3 ,  Jianlin Ren  3  6  7
Affiliations
  • 1. Department of Gastroenterology, The National Key Clinical Specialty, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361005, Fujian Province, P. R. China. [email protected].
  • 2. Xiamen Key Laboratory of Intestinal Microbiome and Human Health, Clinical Research Center for Gut Microbiota and Digestive Diseases of Fujian Province, Xiamen, 361005, Fujian Province, P. R. China. [email protected].
  • 3. Department of Gastroenterology, The National Key Clinical Specialty, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361005, Fujian Province, P. R. China.
  • 4. Department of Gastroenterology, Zhongshan Hospital Xiamen Branch, Fudan University, Xiamen, 361015, Fujian Province, P. R. China.
  • 5. Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, Guangdong, P. R. China.
  • 6. Xiamen Key Laboratory of Intestinal Microbiome and Human Health, Clinical Research Center for Gut Microbiota and Digestive Diseases of Fujian Province, Xiamen, 361005, Fujian Province, P. R. China.
  • 7. Department of Digestive Disease, Institute for Microbial Ecology, School of Medicine, Xiamen University, Xiamen, 361102, Fujian Province, P. R. China.
  • # Contributed equally.
PMID: 42289496 DOI: 10.1007/s00439-026-02845-2
Abstract

Pancreatic Cancer cell metastasis is a major factor influencing prognosis. A Ras homologue member I (ARHI) was reported to regulate proliferation and Apoptosis in pancreatic cancer; however, its role in invasion remains unclear. This study aimed to explore the role and related mechanisms of ARHI in pancreatic Cancer metastasis. We revealed that in pancreatic Cancer ARHI expression levels were consistent with aggressive cellular phenotypes, and that changes in endogenous ARHI protein expression led to corresponding alterations in epithelial-mesenchymal transition (EMT) markers. Furthermore, ARHI accelerated tumor invasion in pancreatic Cancer cells and in a mouse hepatic metastasis model. Notably, this unusual promoting effect of ARHI on EMT and invasion in pancreatic Cancer was primarily exerted through the Notch-1 signaling pathway. Collectively, our findings provide insight into the function and molecular mechanisms of ARHI in pancreatic Cancer metastasis.

Products