Silencing CTNND1 Mediates Triple-Negative Breast Cancer Bone Metastasis via Upregulating CXCR4/CXCL12 Axis and Neutrophils Infiltration in Bone

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

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


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

University Staff: Request a correction | Repository Editors: Update this record

University Of Gloucestershire

Bookmark and Share

Find Us On Social Media:

Social Media Icons Facebook Twitter Google+ YouTube Pinterest Linkedin

Other University Web Sites

University of Gloucestershire, The Park, Cheltenham, Gloucestershire, GL50 2RH. Telephone +44 (0)844 8010001.