HSP47 promotes metastasis of breast cancer by interacting with myosin IIA via the unfolded protein response transducer IRE1α

Breast cancer (BC) is an aggressive cancer that is a leading cause of cancer-associated death in women worldwide. Although increased expression of heat shock protein 47 (HSP47), a collagen-specific chaperone, is associated with the high malignancy of BC, its role in BC remains largely unclear. Here we show that a small population of high-invasive BC cells expresses HSP47 and that HSP47-positive high-invasive BC cells have a high metastatic potential that is completely abolished by disruption of HSP47. HSP47 interacts with non-muscle myosin IIA (NMIIA) via the unfolded protein response transducer IRE1 alpha, resulting in enhancement of the metastatic potential of high-invasive BC cells by augmenting the contractile force of actin filaments. Ablation of NMIIA abrogates the metastatic potential of HSP47-positive high-invasive BC cells. We further show that forced expression of NMIIA confers a high metastatic potential on low-invasive BC cells in which HSP47 but not NMIIA is expressed. Overall, our study indicates that HSP47 acts as a stimulator for metastasis of BC cells and suggest that HSP47 may be a candidate for a therapeutic target against BC.