The Activity of Kv 11.1 Potassium Channel Modulates F-Actin Organization During Cell Migration of Pancreatic Ductal Adenocarcinoma Cells

Manoli, S.; Coppola, S.; Duranti, C.; Lulli, M.; Magni, L.; Kuppalu, N.; ... ; Arcangeli, A. (2019)

Article / Letter to editor

Cell migration exerts a pivotal role in tumor progression, underlying cell invasion and metastatic spread. The cell migratory program requires f-actin re-organization, generally coordinated with the assembly of focal adhesions. Ion channels are emerging actors in regulating cell migration, through different mechanisms. We studied the role of the voltage dependent potassium channel K_V11.1 on cell migration of pancreatic ductal adenocarcinoma (PDAC) cells, focusing on its effects on f-actin organization and dynamics. Cells were cultured either on fibronectin (FN) or on a desmoplastic matrix (DM) with the addition of a conditioned medium produced by pancreatic stellate cells (PSC) maintained in hypoxia (Hypo-PSC-CM), to better mimic the PDAC microenvironment. K_V11.1 was essential to maintain stress fibers in a less organized arrangement in cells cultured on FN. When PDAC cells were cultured on DM plus Hypo-PSC-CM, K_V11.1 activity determined the organization of cortical f-actin into sparse and long filopodia, and allowed f-actin polymerization at a high speed. In both conditions, blocking K_V11.1 impaired PDAC cell migration, and, on cells cultured onto FN, the effect was accompanied by a decrease of basal intracellular Ca²⁺ concentration. We conclude that K_V11.1 is implicated in sustaining pro-metastatic signals in pancreatic cancer, through a reorganization of f-actin in stress fibers and a modulation of filopodia formation and dynamics.

• pancreatic cancer
• hERG1
• fibronectin
• desmoplastic matrix
• hypoxia
• focal adhesions
• stress fibers
• filopodia
• integrins
• intracellular Ca2+ concentration

• All authors: Manoli, S.; Coppola, S.; Duranti, C.; Lulli, M.; Magni, L.; Kuppalu, N.; Nielsen, N.; Schmidt, T.; Schwab, A.; Becchetti, A.; Arcangeli, A.
• Date: 2019-01-23
• Journal: Cancers
• Volume: 11
• Issue: 2
• Pages: 135
• DOI: doi:10.3390/cancers11020135