UC San Diego HUMANOID: Center of Excellence in Human Organoid Research reposted this
The UC San Diego Agilent Center of Excellence in Cellular Intelligence 's weekly series--#DidYouKnow--features examples of how you can push the limits of #Measurements-#Across-#Scales. This is our 15th post of this series. #DidYouKnow that #epithelial #morphogenesis requires a delicate balance between cell-cell #adhesion (via #junctions) and cell-#ECM interactions (via molecules such as #integrins). And if this balance is disrupted, it usually leads to epithelial reprogramming in ways to initiate almost all diseases we know (from #cancers, through #fibrosis to #diseases characterized by #inflammation). WHAT WAS DONE: Today's post (👇) continues to showcase how precise measurement of growing spheroids over ~10 days reveals how a mutant protein found in #cancers weakens cell-cell #adhesion and begins to grow in the form of tubes (arrows, bottom left) and that this feature can be corrected by adding #ECM (bottom right) such that #colonies grow as control (WT) #spheroids. HeLa cells were depleted of the WT endogenous protein (by CRISPR) and then transfected to select stable colonies of cells expressing the WT and the cancer-associated mutant protein. The mutant protein displays gain-of-function by being able to bind and modulate tyrosine-phosphorylated G proteins. This finding reveals a fascinating dynamic: with weaker junctions, the mutant cells became more reliant on cell-ECM interactions to regain their architecture. These results underscore the critical role of ECM not only as a structural scaffold but also as a mediator of cellular behavior in challenging conditions. Continuous #imaging and high-throughput [#HTP] exploration of all possible combinations in 96-well mode was key to revealing the importance of #balance to achieve #homeostasis in health, and how oncogenic mutants tip the same. What to know what #oncogene, and which #signaling pathways were the culprit? Stay tuned and follow our #publications. Post credit: Suchismita Roy and Kevin Perry If you want to know more about how xCELLigence RTCA eSIGHT can help with your research, contact us at: Kevin Perry [k3perry@health.ucsd.edu] Link to learn more about the eSIGHT: https://lnkd.in/gAzDis7 How to #access these and other #equipment: https://lnkd.in/g2iChuYf Need help scheduling? Kevin Perry [k3perry@health.ucsd.edu]. #training; #measurement; #biology; #quantitative; #imaging; #Oncogenesis #ExtracellularMatrix #CellAdhesion #BiomedicalResearch #EpithelialMorphogenesis; La Jolla Institute for Immunology Scripps Research UC San Diego