New doctoral thesis maps how tissue stiffness regulates the behaviour of breast cancer cells
Feifei Yan from the Integrative Cardiovascular, Cancer and Ageing Research unit (ICCA), at the Department of Medicine, Huddinge (MedH), defends her thesis titled "Matrix rigidity control of breast cancer cell malignancy", on 10 April 2026. Main supervisor is Staffan Strömblad.
What is the main focus of your thesis?
Our bodies are made up of many different types of cells, but these cells don’t just float around on their own, they’re supported by a complex framework called the extracellular matrix (ECM). Think of the ECM as the scaffolding and glue that holds our tissues together, giving them shape and structure.
In healthy tissue, the ECM is flexible and well-balanced, but in diseases like breast cancer, this scaffolding becomes much stiffer and denser. This stiffening of the ECM is more than just a physical change. It actually sends signals to the cells, encouraging them to behave more aggressively. Scientists have long known that a stiff ECM is linked to the progression of tumors, but exactly how this happens at the molecular level has remained unclear.
The main focus of my thesis is trying to understand how matrix rigidity regulates breast cancer cell behavior and find potential treatment targets.
Which are the most important results?
One of the key findings was that stiff environments boost the production of certain enzymes, especially one called HMGCS1, which helps cancer cells become more aggressive. This process doesn’t happen by simply making more of the enzyme’s genetic blueprint (mRNA); instead, the cells ramp up production at the protein level, controlled by specific signaling pathways inside the cell.
We also found that two other important kinases, IKBKE and MAPK8, act as switches that help cancer cells respond to a stiff ECM. By blocking these kinases, either with genetic tools or drugs, we were able to make the cancer cells behave less aggressively, even in a stiff environment.
Finally, I identified another protein, TNS4, that helps cancer cells anchor themselves to the stiff ECM. When TNS4 or its partners were disrupted, the cancer cells lost their invasive abilities.
How can this new knowledge contribute to the improvement of people’s health?
These discoveries reveal new ways that the physical environment around cancer cells can drive their behavior, and they highlight promising new targets for therapies that could slow or stop the spread of breast cancer by disrupting these molecular signals.
What are your future ambitions?
My immediate goal is to complete my final study on how matrix stiffness controls human breast cancer cell behavior via TNS4 protein. Looking further ahead, I hope I can work as a clinical scientist and use these mechanical insights to develop smarter, more personalized ways to treat cancer.
Dissertation
Friday 10 April, 10:00, DNA in Neo, Blickagången 16, Campus Flemingsberg.