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HSP47 promotes metastasis of breast cancer by interacting with myosin IIA via the unfolded protein response transducer IRE1α.
- Source :
-
Oncogene [Oncogene] 2020 Jun; Vol. 39 (23), pp. 4519-4537. Date of Electronic Publication: 2020 May 04. - Publication Year :
- 2020
-
Abstract
- 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 IRE1α, 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.
- Subjects :
- Animals
Cell Line, Tumor
Extracellular Matrix metabolism
Female
HSP47 Heat-Shock Proteins genetics
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Metastasis pathology
Nonmuscle Myosin Type IIA genetics
RNA Interference
RNA, Small Interfering genetics
Signal Transduction
Tumor Microenvironment physiology
Unfolded Protein Response physiology
Breast Neoplasms pathology
Endoribonucleases metabolism
HSP47 Heat-Shock Proteins metabolism
Nonmuscle Myosin Type IIA metabolism
Protein Serine-Threonine Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5594
- Volume :
- 39
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 32366908
- Full Text :
- https://doi.org/10.1038/s41388-020-1311-7