Lipoma Preferred Partner (LPP) Regulates Breast Cancer Cell Migration and Invasion

In 2019, over 220,000 Canadians will be diagnosed with cancer and 82,000 will die of the disease. Approximately 90% of cancer related deaths are the result of metastatic disease. This is indeed the case for breast cancer where metastasis is the deadliest aspect of disease progression. We have implicated the Lipoma Preferred Partner (LPP) protein as an important mechanosensitive integrator of TGFβ-mediated breast cancer cell migration and invasion, two cellular processes that are critical for cancer metastasis. Two important structures that regulate migration and invasion are cellular adhesions (migration) and invadopodia (invasion). Cell-matrix adhesions are dynamic structures that link the extracellular matrix to the internal cytoskeleton. Adhesions are tightly regulated in space and time to control cell migration. In turn, invadopodia are structures that form enabling cells in exit primary tumors, enter the blood stream and enter distant tissues at sites of metastasis. Our work shows that LPP is an important regulator of cell-matrix adhesion and invadopodia formation and substrate degradation in response to TGFβ stimulation. We demonstrate this in several cell breast cancer cell lines including triple negative 4T1 cells. Using biophysical tools and quantitative imaging we link LPP to regulation of cell migration through regulation of adhesion dynamics, mechanosensing, regulation of tension at individual adhesions and invasion on substrates with variable biomechanical properties.