Volume 20, No 11, Nov 2010

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 20 Issue 11, November 2010: 1224-1238

ORIGINAL ARTICLES

Migration-associated secretion of melanoma inhibitory activity at the cell rear is supported by KCa3.1 potassium channels

Jennifer Schmidt¹, Kristin Friebel², Roland Sch鰊herr², Marc G Coppolino³ and Anja-Katrin Bosserhoff¹

¹Institute of Pathology, University of Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany
Correspondence: Anja-Katrin Bosserhoff,(anja.bosserhoff@klinik.uni-regensburg.de)

Malignant melanoma, characterized by invasive local growth and early formation of metastases, is the most aggressive type of skin cancer. Melanoma inhibitory activity (MIA), secreted by malignant melanoma cells, interacts with the cell adhesion receptors, integrins α₄β₁ and α₅β₁, facilitating cell detachment and promoting formation of metastases. In the present study, we demonstrate that MIA secretion is confined to the rear end of migrating cells, while in non-migrating cells MIA accumulates in the actin cortex. MIA protein takes a conventional secretory pathway including coat protein complex I (COPI)- and coat protein complex II (COPII)-dependent protein transport to the cell periphery, where its final release depends on intracellular Ca²⁺ ions. Interestingly, the Ca²⁺-activated K⁺-channel, subfamily N, member 4 (KCa3.1), known to be active at the rear end of migrating cells, was found to support MIA secretion. Secretion was diminished by the specific KCa3.1 channel inhibitor TRAM-34 and by expression of dominant-negative mutants of the channel. In summary, we have elucidated the migration-associated transport of MIA protein to the cell rear and also disclosed a new mechanism by which KCa3.1 potassium channels promote cell migration.

Cell Research (2010) 20:1224-1238. doi:10.1038/cr.2010.121; published online 24 August 2010

FULL TEXT | PDF

Browse 2305