Menin regulates YBX1 nucleus translocation to boost the HKDC1 transcription and affect pancreatic cancer glycolysis

Pancreatic ductal adenocarcinoma (PDAC) has a bleak prognosis, often driven by aberrant metabolic reprogramming, particularly glycolysis. This study investigated Menin's role in PDAC metabolism. We found that Menin overexpression significantly suppressed glycolytic markers and activity in PDAC cell lines, a suppression that was reversed by HKDC1 knockdown. Mechanistically, Menin interacts with YBX1, facilitating its nuclear translocation to enhance HKDC1 transcription. In vivo, Menin overexpression inhibited tumor growth and glycolysis in xenograft models. These findings indicate that Menin is a critical regulator of PDAC metabolism through the Menin-YBX1-HKDC1 axis, suggesting its potential as a therapeutic target for pancreatic cancer.