Investigating the role of Kv1.3 channels in lipid metabolism regulation in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers worldwide, characterized by a 5-year survival rate of less than 10%, making the discovery of new druggable target of utmost importance to improve patients prognosis. In this context, voltage-gated potassium channel Kv1.3 is a promising new target. Indeed, it is overexpressed in PDAC samples in patients and the specific inhibition of mitochondrial Kv1.3 is able to inhibit tumor growth in orthotopic models of PDAC. KPCY cells knock-down for Kv1.3 were employed to assess the role of this channel in PDAC progression, focusing on its impact on mitochondrial function and metabolic pathways. Preliminary findings indicate that Kv1.3 KD induces a marked alteration in mitochondrial ultrastructure and a deregulation of protein of the OXPHOS pathway. Additionally, the disruption of Kv1.3 expression leads to altered lipid metabolic processes, with a marked alteration in key proteins regulating lipid synthesis and degradation. This suggests that Kv1.3 may play a role in the metabolic reprogramming of PDAC cells, offering potential new insights into therapeutic strategies targeting mitochondrial ion channels in PDAC.