Contributions of ADAM12 via HB‑EGF/EGFR signaling cascades to EMT and cancer progression in pancreas

Pancreatic cancer (PC) is among the most aggressive malignancies, with a five-year survival rate of <7% in China. The substantial stromal component and activation of epithelial-mesenchymal transition (EMT) in PC contribute to drug resistance and poor outcomes. Between January 2017 and December 2020, 62 pancreatic specimens were obtained via surgical resection from two hospitals. In alignment with the GEPIA database, the expression levels of a disintegrin and metalloproteinase 12 (ADAM12) and heparin-binding epidermal growth factor (HB-EGF) were significantly elevated in 43 PC tissues compared with 19 benign pancreatic masses. Furthermore, elevated expression of ADAM12 and HB-EGF was significantly associated with lymph node metastasis, advanced TNM stage, and reduced survival rates. Additionally, high ADAM12 expression was correlated with the upregulation of EGFR and EMT markers. Collectively, the present findings suggested that ADAM12 is involved in PC progression and may facilitate the shedding of HB-EGF, thereby inducing EMT through the EGFR pathway. These results suggest that targeting the ADAM12/HB-EGF/EGFR signaling pathway could represent a potential therapeutic strategy, warranting further <i>in vivo</i> and <i>in vitro</i> investigations to elucidate the underlying mechanisms.