論文 - 詳細
| RRC ID | 85103 |
|---|---|
| 著者 | Nakayama H, Murakami A, Nishida-Fukuda H, Fukuda S, Matsugi E, Nakahara M, Kusumoto C, Kamei Y, Higashiyama S. |
| タイトル | Semaphorin 3F inhibits breast cancer metastasis by regulating the Akt-mTOR and TGFβ signaling pathways via neuropilin-2. |
| ジャーナル | Sci Rep |
| Abstract |
Class 3 semaphorins are axon guidance factors implicated in tumor and vascular biology, including invasive activity. Recent studies indicate that semaphorin 3F (SEMA3F) is a potent inhibitor of metastasis; however, its functional role in breast cancer is not fully understood. We found that exogenous SEMA3F inhibited phosphorylation of Akt and mTOR downstream kinase S6K in MDA-MB-231 and MCF7 cells via neuropilin-2 (NRP2) receptor. We also examined the effect of SEMA3F on breast cancer progression in vivo allograft model. The mouse 4T1 breast cancer cells or 4T1 cells overexpressing SEMA3F (4T1-SEMA3F) were implanted into mammary fat pads of Balb/c mice. We found that tumor growth was significantly inhibited in 4T1-SEMA3F injected mice compared to controls. Immunostaining revealed a remarkable reduction in the expression of vimentin, a mesenchymal cell marker, in 4T1-SEMA3F tumors. We also observed that mice injected with 4T1-SEMA3F cells had minimal metastasis to the liver and lungs, compared to controls. As a novel feature, SEMA3F suppressed TGFβ-induced Smad2 phosphorylation, resulting in the inhibition of cell invasiveness and epithelial-to-mesenchymal transition (EMT) in breast cancer. Consistently, a significant correlation between reduced expression of SEMA3F and poor outcome in patients with breast cancer. We conclude that SEMA3F acts as a dual inhibitor of the Akt-mTOR and TGFβ signaling pathways; thus, it has the potential to treat metastatic breast cancer. |
| 巻・号 | 15(1) |
| ページ | 7394 |
| 公開日 | 2025-3-3 |
| DOI | 10.1038/s41598-025-91559-y |
| PII | 10.1038/s41598-025-91559-y |
| PMID | 40033046 |
| PMC | PMC11876635 |
| MeSH | Animals Breast Neoplasms* / genetics Breast Neoplasms* / metabolism Breast Neoplasms* / pathology Cell Line, Tumor Female Humans MCF-7 Cells Membrane Proteins* / genetics Membrane Proteins* / metabolism Mice Mice, Inbred BALB C Neoplasm Metastasis Nerve Tissue Proteins* / genetics Nerve Tissue Proteins* / metabolism Neuropilin-2* / metabolism Phosphorylation Proto-Oncogene Proteins c-akt* / metabolism Signal Transduction* TOR Serine-Threonine Kinases* / metabolism Transforming Growth Factor beta* / metabolism |
| IF | 3.998 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) |