Sustained Shugoshin 1 downregulation reduces tumor growth and metastasis in a mouse xenograft tumor model of triple-negative breast cancer.
Epithelial-to-mesenchymal transition
Metastasis
Mitosis
SGO1
Triple-negative breast cancer
Tumor growth
Journal
Cell division
ISSN: 1747-1028
Titre abrégé: Cell Div
Pays: England
ID NLM: 101251560
Informations de publication
Date de publication:
30 Apr 2023
30 Apr 2023
Historique:
received:
30
09
2022
accepted:
11
04
2023
medline:
1
5
2023
pubmed:
1
5
2023
entrez:
30
4
2023
Statut:
epublish
Résumé
Triple-negative breast cancer (TBNC) is an aggressive breast cancer subtype with a poor prognosis. Shugoshin-1 (SGO1) protects chromatids from early separation. Previous studies from our group have demonstrated that transient SGO1 downregulation suppresses early stages of metastasis (the epithelial-to-mesenchymal transition, or EMT, cell invasion, and cell migration) in TNBC cells. Thus, the inhibition of SGO1 activity may represent a potential therapeutic intervention against cancers that progress to metastasis. Therefore, we aimed to investigate the effects of sustained shRNA-mediated SGO1 downregulation on tumor growth and metastasis in TBNC. To that end, female NOD-SCID Gamma (NSG) mice were injected with 2.5 × 10 Tumor growth and metastasis to the lymph nodes and lungs were significantly reduced in the shRNA SGO1-treated mice group, while metastasis to the liver tends to be lower in cells with downregulated SGO1, but it did not reach statistical significance. Furthermore, sustained SGO1 downregulation significantly reduced cell proliferation, cell migration, and invasion which correlated with lower levels of Snail, Slug, MMP2, MMP3, and MMP9. The supression of SGO1 activity in TNBC harboring dysregulated expression of SGO1 may be a potential target for preventing breast cancer growth and metastasis.
Sections du résumé
BACKGROUND
BACKGROUND
Triple-negative breast cancer (TBNC) is an aggressive breast cancer subtype with a poor prognosis. Shugoshin-1 (SGO1) protects chromatids from early separation. Previous studies from our group have demonstrated that transient SGO1 downregulation suppresses early stages of metastasis (the epithelial-to-mesenchymal transition, or EMT, cell invasion, and cell migration) in TNBC cells. Thus, the inhibition of SGO1 activity may represent a potential therapeutic intervention against cancers that progress to metastasis. Therefore, we aimed to investigate the effects of sustained shRNA-mediated SGO1 downregulation on tumor growth and metastasis in TBNC. To that end, female NOD-SCID Gamma (NSG) mice were injected with 2.5 × 10
RESULTS
RESULTS
Tumor growth and metastasis to the lymph nodes and lungs were significantly reduced in the shRNA SGO1-treated mice group, while metastasis to the liver tends to be lower in cells with downregulated SGO1, but it did not reach statistical significance. Furthermore, sustained SGO1 downregulation significantly reduced cell proliferation, cell migration, and invasion which correlated with lower levels of Snail, Slug, MMP2, MMP3, and MMP9.
CONCLUSION
CONCLUSIONS
The supression of SGO1 activity in TNBC harboring dysregulated expression of SGO1 may be a potential target for preventing breast cancer growth and metastasis.
Identifiants
pubmed: 37122033
doi: 10.1186/s13008-023-00088-5
pii: 10.1186/s13008-023-00088-5
pmc: PMC10150544
doi:
Types de publication
Journal Article
Langues
eng
Pagination
6Subventions
Organisme : NIGMS NIH HHS
ID : R25 GM082406
Pays : United States
Organisme : NIMHD NIH HHS
ID : U54 MD007579
Pays : United States
Organisme : NIGMS NIH HHS
ID : U54 GM133807
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA163068
Pays : United States
Organisme : NIMHD NIH HHS
ID : U54 MD007587
Pays : United States
Organisme : NIH HHS
ID : CA163071
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA266046
Pays : United States
Organisme : NIH HHS
ID : U54GM133807
Pays : United States
Organisme : NIH HHS
ID : R25GM096955
Pays : United States
Organisme : NIH HHS
ID : R01CA266046
Pays : United States
Organisme : NIH HHS
ID : F31CA247459
Pays : United States
Organisme : NIMHD NIH HHS
ID : G12 MD007579
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA163071
Pays : United States
Organisme : NCI NIH HHS
ID : F31 CA247459
Pays : United States
Informations de copyright
© 2023. The Author(s).
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