scholarly journals Rapid Changes in Connexin-43 in Response to Genotoxic Stress Stabilize Cell–Cell Communication in Corneal Endothelium

2011 ◽  
Vol 52 (8) ◽  
pp. 5174 ◽  
Author(s):  
Danny S. Roh ◽  
James L. Funderburgh
1994 ◽  
Vol 50 (2) ◽  
pp. 377-389 ◽  
Author(s):  
Chimaraoke Nnamani ◽  
Angela Godwin ◽  
Charles A. Ducsay ◽  
Lawrence D. Longo ◽  
William H. Fletcher

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yong-Li Dong ◽  
Gangadhara P. Vadla ◽  
Jin-Yu (Jim) Lu ◽  
Vakil Ahmad ◽  
Thomas J. Klein ◽  
...  

AbstractOncogenic RAS mutations are associated with tumor resistance to radiation therapy. Cell-cell interactions in the tumor microenvironment (TME) profoundly influence therapy outcomes. However, the nature of these interactions and their role in Ras tumor radioresistance remain unclear. Here we use Drosophila oncogenic Ras tissues and human Ras cancer cell radiation models to address these questions. We discover that cellular response to genotoxic stress cooperates with oncogenic Ras to activate JAK/STAT non-cell autonomously in the TME. Specifically, p53 is heterogeneously activated in Ras tumor tissues in response to irradiation. This mosaicism allows high p53-expressing Ras clones to stimulate JAK/STAT cytokines, which activate JAK/STAT in the nearby low p53-expressing surviving Ras clones, leading to robust tumor re-establishment. Blocking any part of this cell-cell communication loop re-sensitizes Ras tumor cells to irradiation. These findings suggest that coupling STAT inhibitors to radiotherapy might improve clinical outcomes for Ras cancer patients.


Oncotarget ◽  
2016 ◽  
Vol 7 (19) ◽  
pp. 26966-26978 ◽  
Author(s):  
Junjie Gao ◽  
Tak Sum Cheng ◽  
An Qin ◽  
Nathan J. Pavlos ◽  
Tao Wang ◽  
...  

2020 ◽  
Author(s):  
Rachael P. Norris ◽  
Mark Terasaki

AbstractGap junctions have well-established roles in cell-cell communication by way of forming permeable intercellular channels. Less is understood about their internalization, which forms double membrane vesicles containing cytosol and membranes from another cell, called connexosomes or annular gap junctions. Here, we systematically studied the fate of connexosomes in intact ovarian follicles. High pressure frozen, serial sectioned tissue was immunogold labeled for Connexin 43. Within a volume of electron micrographs, every labeled structure was categorized and counted. Surface area measurements indicate that large connexosomes undergo fission. Subsequent modifications are separation of inner and outer membranes, loss of Cx43 from the outer membrane, and outward budding of the modified membranes. We also documented several clear examples of organelle transfer from one cell to another by gap junction internalization. We discuss how connexosome formation and processing may be a novel means for gap junctions to mediate cell-cell communication.


Oncotarget ◽  
2019 ◽  
Vol 10 (40) ◽  
pp. 4079-4079
Author(s):  
Junjie Gao ◽  
Tak Sum Cheng ◽  
An Qin ◽  
Nathan J. Pavlos ◽  
Tao Wang ◽  
...  

2020 ◽  
Author(s):  
Yong-Li Dong ◽  
Ganghadara P Valdka ◽  
Jin-Yu (Jim) Lu ◽  
Vakil Ahmad ◽  
Thomas J. Klein ◽  
...  

AbstractOncogenic RAS mutations are associated with tumor resistance to radiation therapy. The underlying mechanisms remain unclear. Emergent cell-cell interactions in the tumor microenvironment (TME) profoundly influence therapy outcomes. The nature of these interactions and their role in Ras tumor radioresistance remain unclear. We used Drosophila oncogenic Ras tissues and human Ras cancer cell radiation models to address these questions. We discovered that cellular response to genotoxic stress cooperates with oncogenic Ras to activate JAK/STAT non-cell autonomously in the TME. JAK/STAT accelerates the growth of the less-damaged Ras tumor cells, leading to rapid tumor recurrence. Specifically, p53 is heterogeneously activated in Ras tumor tissues in response to irradiation. This mosaicism allows high p53-expressing Ras clones to stimulate JAK/STAT cytokines, which activate JAK/STAT in the nearby low p53-expressing surviving Ras clones, leading to robust tumor re-establishment. Blocking any part of this cell-cell communication loop re-sensitizes Ras tumor cells to irradiation. This finding suggests that coupling STAT inhibitors to radiotherapy might improve clinical outcomes for Ras cancer patients.


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