Engagement, reception and breakup: Three steps of cell motility regulated by HPIP signaling

Abstract

Tumor metastasis is the prime cause for increased morbidity and mortality for majority of the cancers. Invasive or infiltrative ductal carcinoma (IDC) is the predominant form of breast cancer, accounting approximately 80% of all breast cancers. The molecular portraits and the mechanism by which they promote IDC remain largely unknown. Hematopoietic PBX interacting protein (HPIP/PBXIP1), a microtubule binding protein, regulates cancer cell migration and invasion. However, functional mechanism underlying HPIP-mediated cell migration in cancer remains uncertain. Here, we describe our recent studies in which we identified the new mechanisms by which HPIP regulates cell migration in breast cancer cells. Our recent studies confirmed that HPIP expression is elevated in breast infiltrative ductal carcinoma and positively correlated with poor patient survival. We reported that HPIP directly interacts and activates FAK to promote the cell migration. Mechanistic studies further revealed that HPIP induces focal adhesion disassembly by enhancing calpain2 activity through MAPK pathway that led to talin proteolysis, focal adhesion turnover and cell migration. Interestingly, the activated calpain2 in turn cleaves HPIP suggesting the tight regulation of HPIP-FAK-calpain2 signaling cascade during cell migration.