Mechanobiology in Cancer

DCIS progression

Cancer cells do not become invasive by genetics alone—the plasma membrane is a decision-making hub that translates mechanical stress into biochemical programs. In ductal carcinoma in situ (DCIS), the non-invasive breast cancer, proliferative crowding inside ducts imposes persistent mechanical load. Our work shows that this stress inactivates the mechanosensitive channel TRPV4 and drives its relocation to the plasma membrane together with key ion-transport machinery. The result is a rapid, transcription-independent reorganization of cortical tension and cell shape that licenses escape from the duct. Understanding these disease mechanisms is essential for patient care because it clarifies which DCIS lesions are likely to progress and why.

Building on the findings summarized in our eLife study, we are quantifying how crowding and osmotic shifts compartmentalize the membrane, how TRPV4 and other channel/transporter trafficking restores ionic balance during stress, how DCIS cells survive and evade immune surveillance, and how these physical states correlate with patient outcomes in longitudinal cohorts. This program integrates deterministic biophysics, super-resolution imaging, and pathology to connect mechanism to progression risk. 

HER2 overexpression and metastasis

We also investigate how HER2 overexpression couples to this mechanical program. Our data suggest that HER2 becomes enriched in stress-defined membrane domains where signaling is amplified. This synergy—mechanical priming plus HER2 enrichment—offers a mechanistic basis for aggressive behavior and metastatic competence. We are currently addressing this using our multi-angle-crossing structured illumination microscopy (MAxSIM) based biophysical and cell biology methods.