RRC ID 65161
著者 Sakabe T, Wakahara M, Shiota G, Umekita Y.
タイトル Role of cytoplasmic localization of maspin in promoting cell invasion in breast cancer with aggressive phenotype.
ジャーナル Sci Rep
Abstract 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.
巻・号 11(1)
ページ 11321
公開日 2021-5-31
DOI 10.1038/s41598-021-90887-z
PII 10.1038/s41598-021-90887-z
PMID 34059749
PMC PMC8166868
MeSH Breast Neoplasms / metabolism* Breast Neoplasms / pathology Carcinogenesis Cytoplasm / metabolism Epithelial-Mesenchymal Transition Humans MCF-7 Cells Neoplasm Invasiveness Phenotype Serpins / metabolism* Transforming Growth Factor beta2 / metabolism
IF 3.998
リソース情報
ヒト・動物細胞 MCF7(RCB1904) MDA-MB-453(RCB1192)