Additional supporting information may be found in the online version of this article.
Original Research Article
A dominant negative Cx43 mutant differentially affects tumorigenic and invasive properties in human metastatic melanoma cells†
Article first published online: 20 DEC 2012
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Cellular Physiology
Volume 228, Issue 4, pages 853–859, April 2013
How to Cite
Zucker, S. N., Bancroft, T. A., Place, D. E., Des Soye, B., Bagati, A. and Berezney, R. (2013), A dominant negative Cx43 mutant differentially affects tumorigenic and invasive properties in human metastatic melanoma cells. J. Cell. Physiol., 228: 853–859. doi: 10.1002/jcp.24235
- Issue published online: 20 DEC 2012
- Article first published online: 20 DEC 2012
- Accepted manuscript online: 5 OCT 2012 07:49AM EST
- Manuscript Accepted: 20 SEP 2012
- Manuscript Received: 12 SEP 2012
- National Institutes of Health. Grant Number: GM 07431
Previous reports have implicated connexin 43 (Cx43) as a tumor suppressor in early stages of tumorigenesis and in some cases as an enhancer of cell migration in later stages. To address the role of Cx43 in melanoma tumor progression, we utilized two melanoma cell lines derived from the same patient in pre-metastasis (WM793B) and following isolation from a lung metastasis in nude mice (1205Lu). Our results demonstrate a strikingly increased expression of Cx43 in both the pre-metastatic and metastatic melanoma cell lines that were actively migrating compared to non-migrating cells. To further investigate the role of Cx43 in these melanoma cells, we overexpressed wild type (wt) Cx43 as well as a mutant dominant negative Cx43 mutant that causes closed channels (T154A). The metastatic 1205Lu cells expressing Cx43-T154A showed a twofold decrease in colony formation on soft agar while the nonmetastatic WM793B cells showed no significant change. In invasion assays through a collagen matrix, the same Cx43-T154A 1205Lu cells demonstrated a three- to fourfold increase in the invasion index compared to either wt Cx43 or vector control cells. The increase in invasiveness was eliminated by migration towards media with charcoal-stripped serum, suggesting that migration may be directed towards a lipophilic compound(s). Our findings demonstrate that a dominant negative Cx43 mutant deficient in channel formation exhibits a dual pattern of regulation in metastatic melanoma cells with a decrease in anchorage-independent growth and an increase in invasive potential. J. Cell. Physiol. 228: 853–859, 2013. © 2012 Wiley Periodicals, Inc.