Research

Mechanobiology and Cancer. The specific scientific focus of our center is the mechanobiology of tumor progression in breast cancer.

Mechanobiology seeks to understand how mechanical forces affect proteins, cells and tissues. Mechanical forces change how proteins cluster in membranes, affecting signaling, and also provide specific guidance to cells, helping them to decide where to divide and how to arrange themselves. In related fields such as developmental biology, scientists have long appreciated the role of cell and tissue mechanics. However, the role of mechanics in cancer initiation, progression, and metastasis has received comparatively little attention.

In the 1980's and 1990's, LBNL's Mina Bissell pioneered the idea that a breast cell's microenvironment dramatically influences whether it becomes a cancer cell. It is now appreciated that cancer cells are 'plastic' in the sense that they can change their architecture and function in response to external signals. Phenotypic plasticity reflects the lack of a simple correspondence between the genome of a cell and its current shape, size, metabolism, behavior, and mechanical characteristics.

Triple Negative Breast Cancer.
The center's primary cancer focus is the triple negative subtype of basal breast cancer, which lacks the estrogen, progesterone, and Her2/neu receptors. Patients with this more aggressive, triple negative subtype have fewer treatment options and, overall, a poor prognosis.

Almost a decade ago Mina Bissell (center co-Investigator) and Valerie Weaver (senior co-Investigator and center co-Director) showed that changing signaling between the cell and its microenvironment determines whether a mass of malignant cells invades or reverts to a non-invasive, non-proliferating tissue.

These seminal studies laid the conceptual framework for Weaver's subsequent work illustrating the importance of a dynamic and reciprocal link between intrinsic and extrinsic force on tissue differentiation and tumor invasion. Our center builds upon these paradigm shifting observations indicating that the normal behavior of a cell within a tissue is regulated by force.

Our investigators hypothesize that the malignancy is maintained by exchanges of cells with their microenvironment and that reversion to a less malignant phenotype can occur if these interactions are normalized. We examine how mechanical forces affect cell signaling during tumorigenesis, how tumors change the mechanical characteristics of their tissue environment, and the feedback between cells and their environment.

Among other approaches, we use advanced force probes and imaging techniques to gauge the forces within breast cancer model systems. The integration of these state-of-the-art tools in the physical, theoretical and biological sciences may allow us to clarify the physico-chemical interactions of cancer cells with their microenvironment. Further, cellular plasticity and reversion research may lead to potential therapeutics targeted to the cellular microenvironment.