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Article
Wei Jin
Department of Breast Surgery, Fudan University Shanghai Cancer Center
Corresponding Author
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Metastasis is a major cause of death in individuals suffering from triple-negative breast cancer. Alternative splicing of mRNA precursor allows cancer cells to create different protein isoforms which may promote metastasis. Quantitative proteomic analysis of primary and metastatic breast cancer cells revealed that nuclear speckle-related protein 70 (NSrp70) was significantly downregulated in highly metastatic cells. Downregulation of NSrp70 promoted the migration and invasion of breast cancer cells in vitro and in vivo. Mechanistically, we found that NSrp70 inhibited the skipped exon alternative splicing of NUMB, promoted the degradation of TGF-beta receptor 1(TβR1) through lysosome pathway, and regulated TGFβ/SMAD-mediated epithelial-mesenchymal transition (EMT) phenotype in breast cancer cells. Furthermore, high NSrp70 expression correlated with better prognosis in breast cancer patients. Our findings revealed that splicing regulator NSrp70 may serve as a metastasis suppressor.
Keywords
NSrp70, alternative splicing, breast cancer, metastasis, TGFβ signaling
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This preprint is under consideration at a Nature Portfolio Journal. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Nature journals have partnered with Research Square to offer In Review, a journal-integrated preprint deposition service.
Article
Wei Jin
Department of Breast Surgery, Fudan University Shanghai Cancer Center
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 18 Mar, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Metastasis is a major cause of death in individuals suffering from triple-negative breast cancer. Alternative splicing of mRNA precursor allows cancer cells to create different protein isoforms which may promote metastasis. Quantitative proteomic analysis of primary and metastatic breast cancer cells revealed that nuclear speckle-related protein 70 (NSrp70) was significantly downregulated in highly metastatic cells. Downregulation of NSrp70 promoted the migration and invasion of breast cancer cells in vitro and in vivo. Mechanistically, we found that NSrp70 inhibited the skipped exon alternative splicing of NUMB, promoted the degradation of TGF-beta receptor 1(TβR1) through lysosome pathway, and regulated TGFβ/SMAD-mediated epithelial-mesenchymal transition (EMT) phenotype in breast cancer cells. Furthermore, high NSrp70 expression correlated with better prognosis in breast cancer patients. Our findings revealed that splicing regulator NSrp70 may serve as a metastasis suppressor.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This preprint is available for download as a PDF.
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