Mammary
serine protease inhibitor (
maspin) is a tumor suppressor gene that is downregulated during
carcinogenesis and
breast cancer progression. While the nuclear localization of
maspin is essential for
tumor suppression, we previously reported that the cytoplasmic localization of
maspin was significantly correlated with poor prognosis in
breast cancer patients. To understand the mechanisms that underlie oncogenic role of cytoplasmic
maspin, we studied its
biological function in
breast cancer cell lines. Subcellular localization of
maspin in MDA-MB-231
breast cancer cells was mainly detected in the cytoplasm, whereas in MCF10A mammary epithelial cells,
maspin was present in both cytoplasm and nucleus. In MDA-MB-231 cells,
maspin overexpression promoted cell proliferation and cell invasion, whereas
maspin downregulation resulted in the opposite effect. Further, we observed that SRGN
protein levels were increased in MDA-MB-231 cells stably overexpressing
maspin. Finally,
maspin overexpression in MDA-MB-231 cells resulted in the
N-cadherin and epithelial mesenchymal transition (EMT)-related
transcription factors upregulation, and TGFβ signaling pathway activation. These results suggested that cytoplasmic
maspin enhances the invasive and metastatic potential in
breast cancer cells with aggressive phenotype by inducing EMT via SRGN/TGFβ axis. This study demonstrated a novel
biological function of cytoplasmic
maspin in progression of
breast cancer cells with an aggressive phenotype.