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Lin, Qun, Fang, Xiaolin, Liang, Gehao, Luo, Qing, Cen, Yinghuan, Shi, Yu, Jia, Shijie, Li, Juanmei, Yang, Wenqian, Sanders, Andrew 
ORCID: 0000-0002-7997-5286, Gong, Chang and Jiang, Wenguo
(2021)
Silencing CTNND1 Mediates Triple-Negative Breast Cancer Bone Metastasis via Upregulating CXCR4/CXCL12 Axis and Neutrophils Infiltration in Bone.
Cancers, 13 (22).
ART 5703.
doi:10.3390/cancers13225703
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11404_Sanders_Lin_Fang_Liang_Luo_Cen_Shi_Jia_Li_Yang_Gong_Jiang_(2021)_Silencing_CTNND1_mediates_triple_negative_breast_cancer_bone_metastatis_via_upregulating_CXCR4_CXCL12_axis_and_neutrophils_infriltration_in_bone.pdf - Published Version Available under License Creative Commons Attribution 4.0. Download (11MB) | Preview |
Abstract
Bone metastasis from triple-negative breast cancer (TNBC) frequently results in poorer prognosis than other types of breast cancer due to the delay in diagnosis and intervention, lack of effective treatments and more skeletal-related complications. In the present study, we identified CTNND1 as a most reduced molecule in metastatic bone lesion from TNBC by way of high throughput sequencing of TNBC samples. In vivo experiments revealed that knockdown of CTNND1 enhanced tumor cells metastasis to bones and also increased neutrophils infiltration in bones. In vitro, we demonstrated that knockdown of CTNND1 accelerated epithelial–mesenchymal transformation (EMT) of tumor cells and their recruitment to bones. The involvement by CTNND1 in EMT and bone homing was achieved by upregulating CXCR4 via activating the PI3K/AKT/HIF-1αpathway. Moreover, TNBC cells with reduced expression of CTNND1 elicited cytotoxic T-cells responses through accelerating neutrophils infiltration by secreting more GM-CSF and IL-8. Clinically, patients with triple-negative breast cancer and lower level of CTNND1 had shorter overall survival (OS) and distant metastasis-free survival (DMFS). It was concluded that downregulation of CTNND1 played a critical role in facilitating bone metastasis of TNBC and that CTNND1 might be a potential biomarker for predicting the risk of bone metastases in TNBC.
| Item Type: | Article |
|---|---|
| Article Type: | Article |
| Uncontrolled Keywords: | CTNND1; Bone metastasis; Epithelial–mesenchymal transformation; CXCR4; Neutrophils |
| Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
| Divisions: | Schools and Research Institutes > School of Education and Science |
| Research Priority Areas: | Place, Environment and Community |
| Depositing User: | Anna Kerr |
| Date Deposited: | 28 Jul 2022 09:58 |
| Last Modified: | 16 Oct 2023 10:10 |
| URI: | https://eprints.glos.ac.uk/id/eprint/11404 |
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