Breast Cancer Metastasis Research Group

Elucidating the Signaling and Transcriptional Pathways Underlying Osteolytic Breast Cancer Bone Metastasis 

Metastatic disease remains the second-leading cause of death in cancer patients. Cancer cells will leave the primary tumor site and establish secondary tumors in distant organs. In breast cancer, the formation of aggressive bone metastases is most common and is associated with severe skeletal complications, including osteolytic bone destruction, increase fractures, chronic pain, and reduced patient survival. Preliminary work in our lab suggests that bone-metastatic breast cancer cells acquire mechano-memory, a state where memory of past environmental stiffness and prolonged biophysical cues is retained, driving changes in the cells’ future behavior, signaling networks and gene expression. 

ATAC-seq and proteomic analyses will be performed to elucidate the epigenetic and proteomic changes induced by priming of breast cancer cells on soft and stiff ECM substrates that underlie the observed mechanomemory. My proposed project will build on this study by functionally validating the signaling and transcriptional pathways enriched in stiff-trained cells.