Seminar: Prof. Dale W. Laird

The emergence of pannexins and their putative role in melanomas

Date:
11 September 2013 00:00 hrs.
Location:
Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289
Title:
The emergence of pannexins and their putative role in melanomas
Speaker(s):

Prof. Dale W. Laird, Department of Anatomy and Cell Biology, University of Western Ontario, Canada

 

Host(s):

Prof. Peter Friedl, Department of Cell Biology, NCMLS

11-09-2013 00:00:00Europe/AmsterdamThe emergence of pannexins and their putative role in melanomas Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289Rimlsrimls@radboudumc.nl

Remarks / more information:

Dale _w _lairdPannexins (Panx) are a novel family of three channel forming glycoproteins. Panx1 is ubiquitously expressed in mammalian organs and forms a functional channel for ATP release. Panx1-mediated ATP release upon activation by caspase cleavage was shown to act as a "find-me" signal for thymocyte clearance by macrophages in a recent Nature paper that we co-authored.  

Malignant melanoma is one of the most deadly cancers accounting for ~79% of all skin cancer-related deaths. Our data indicated that Panx1 is expressed at low levels in skin melanocytes and is highly upregulated in malignant melanoma cells. Panx1 levels were further found to be positively correlated with the aggressiveness of B16 isogenic melanoma cell lines. Upon Panx1-knockdown, melanoma cells resemble normal melanocytes in cell morphology and melanin production, exhibiting reduced migration and growth. In vivo, Panx1-depleted cells formed smaller melanoma tumors in the chick chorioallantoic membrane and had significantly reduced metastasis to the liver of the avian embryos. Therefore, we propose that Panx1 is significantly up-regulated as melanocytes transform into melanomas and, moreover, a targeted knockdown of Panx1 can reduce the tumorigenic properties of melanomas. We hypothesize that Panx1 acts as a proto-oncogene in melanocyte transformation and is a viable therapeutic target in the prevention of melanoma disease progression.



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