Mariya Mardamshina, Shiri Karagach, Vishnu Mohan, Gali Arad , Daniela Necula, Ofra Golani, Liat Fellus-Alyagor, Anjana Shenoy, Kateryna Krol, Daniel Pirak, Nitay Itzhacky, Irina Marin, Bruria Shalmon, Yoseph Addadi, Roded Sharan, Einav Gal-Yam, Iris Barshack& Tamar Geiger
Cancer cells are not locked into a single identity. In different environments, they can change how they function, the proteins they produce, how aggressive they are, and they can even become resistant to therapy. This ability to shape shift is called phenotypic plasticity.
Plasticity may help explain why breast cancer tumors vary so much between patients. Even within the same subgroup, tumors can differ, and while genetic differences are well studied, less is known about protein changes and what drives them.
One factor that might be responsible is the tumor microenvironment. This refers to the cells, signals, and proteins surrounding a tumor. This environment can determine which genes are turned on and which proteins are made.
To explore this idea, scientists mapped protein location and abundance across different regions in 33 tumors. They found that while genetics can drive tumor growth, the microenvironment also shapes cancer cell behavior. In areas with high amounts of immune cells, cancer cells express proteins that help them evade the immune system. In areas with low immune activity, cancer cells take on a more aggressive state.
This work shows that cancer is not simply a genetic disease. Different regions of a tumor have different environments, and cancer cells adopt distinct proteins and functions to survive in these environments. Understanding this relationship can explain how cancer becomes resistant, and help scientists develop more targeted cancer therapies.
