Richard White: What Triggers Changes in Cancer Cell State?
Richard White, Physician-Scientist, Oncologist, and Professor at the University of Oxford, shared a post on X about a paper he co-authored with colleagues published in Nature:
“Cancer cells are notoriously plastic, but what triggers the changes in cell state?
In our new Nature paper, Miranda Hunter found that mechanical pressure is a key to this switch.
Using a combination of zebrafish and human melanoma cells, she discovered that when cells are mechanically confined, this turns up chromatic factors like HMGB2, rewiring them to be more invasive and drug resistant. An especially cool part of the story is connecting it to the LINC complex, which acts as a bridge from the outside of the cell to the nucleus.
The implications are pretty clear: while DNA mutations and chemical signals from the environment are important, physical pressure is just as important in letting cancer cells take on new behaviours. Although we found this in melanoma, the same thing seems to happen in other cancers like the pancreas and the brain.
My favorite part? This was driven by Miranda’s curiosity. She noticed that the cells in the tumor looked squeezed, and then followed the trail all the way to the mechanism and implications.
And a special thanks to our many collaborators and funding from the Melanoma Research Alliance, Pershing Square Sohn Cancer Research Alliance (PSSCRA), NIH Common Fund, the NCI, and Ludwig Cancer.”
Title: Mechanical confinement governs phenotypic plasticity in melanoma
Authors: Miranda V. Hunter, Eshita Joshi, Sydney Bowker, Emily Montal, Yilun Ma, Young Hun Kim, Zhifan Yang, Laura Tuffery, Zhuoning Li, Eric Rosiek, Alexander Browning, Reuben Moncada, Itai Yanai, Helen Byrne, Mara Monetti, Elisa de Stanchina, Pierre-Jacques Hamard, Richard P. Koche, Richard M. White
You can read the Full Article in Nature.
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