Human ether à-gogo K(+) channel 1 (hEag1) regulates MDA-MB-231 breast cancer cell migration through Orai1-dependent calcium entry.

Abstract

Breast cancer (BC) has a poor prognosis due to its strong metastatic ability. Accumulating data present ether à go-go (hEag1) K(+) channels as relevant player in controlling cell cycle and proliferation of non-invasive BC cells. However, the role of hEag1 in invasive BC cells migration is still unknown. In this study, we studied both the functional expression and the involvement in cell migration of hEag1 in the highly metastatic MDA-MB-231 human BC cells. We showed that hEag1 mRNA and proteins were expressed in human invasive ductal carcinoma tissues and BC cell lines. Functional activity of hEag1 channels in MDA-MB-231 cells was confirmed using astemizole, a hEag1 blocker, or siRNA. Blocking or silencing hEag1 depolarized the membrane potential and reduced both Ca(2+) entry and MDA-MB-231 cell migration without affecting cell proliferation. Recent studies have reported that Ca(2+) entry through Orai1 channels is required for MDA-MB-231 cell migration. Down-regulation of hEag1 or Orai1 reduced Ca(2+) influx and cell migration with similar efficiency. Interestingly, no additive effects on Ca(2+) influx or cell migration were observed in cells co-transfected with sihEag1 and siOrai1. Finally, both Orai1 and hEag1 are expressed in invasive breast adenocarcinoma tissues and invaded metastatic lymph node samples (LNM(+)). In conclusion, this study is the first to demonstrate that hEag1 channels are involved in the serum-induced migration of BC cells by controlling the Ca(2+) entry through Orai1 channels. hEag1 may therefore represent a potential target for the suppression of BC cell migration, and thus prevention of metastasis development.

• Authors: Mehdi Hammadi, Valérie Chopin, Fabrice Matifat, Isabelle Dhennin-Duthille, Maud Chasseraud, Henri Sevestre, Halima Ouadid-Ahidouch
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 227 Issue 12 Pg. 3837-46 (Dec 2012) ISSN: 1097-4652 [Electronic] United States
• PMID: 22495877 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Wiley Periodicals, Inc.

Chemical References

• Calcium Channels
• Ether-A-Go-Go Potassium Channels
• KCNH1 protein, human
• ORAI1 Protein
• ORAI1 protein, human
• Manganese
• Calcium

Topics

• Breast Neoplasms (metabolism, pathology)
• Calcium (metabolism)
• Calcium Channels (genetics, metabolism)
• Carcinoma, Ductal, Breast (metabolism, pathology)
• Cell Line, Tumor
• Cell Movement (physiology)
• Cell Survival
• Ether-A-Go-Go Potassium Channels (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic (physiology)
• Humans
• Immunohistochemistry
• Lymph Nodes (pathology)
• Manganese
• Neoplasm Invasiveness
• ORAI1 Protein
• Patch-Clamp Techniques
• RNA Interference
• Reverse Transcriptase Polymerase Chain Reaction