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

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 mos...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Qun Lin, Xiaolin Fang, Gehao Liang, Qing Luo, Yinghuan Cen, Yu Shi, Shijie Jia, Juanmei Li, Wenqian Yang, Andrew J. Sanders, Chang Gong, Wenguo Jiang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	CTNND1 bone metastasis epithelial–mesenchymal transformation CXCR4 neutrophils Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/5edc4f6d7c7948a9acf4e1bee4bdf1f2
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5edc4f6d7c7948a9acf4e1bee4bdf1f2
record_format	dspace
spelling	oai:doaj.org-article:5edc4f6d7c7948a9acf4e1bee4bdf1f22021-11-25T17:02:55ZSilencing CTNND1 Mediates Triple-Negative Breast Cancer Bone Metastasis via Upregulating CXCR4/CXCL12 Axis and Neutrophils Infiltration in Bone10.3390/cancers132257032072-6694https://doaj.org/article/5edc4f6d7c7948a9acf4e1bee4bdf1f22021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5703https://doaj.org/toc/2072-6694Bone 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.Qun LinXiaolin FangGehao LiangQing LuoYinghuan CenYu ShiShijie JiaJuanmei LiWenqian YangAndrew J. SandersChang GongWenguo JiangMDPI AGarticleCTNND1bone metastasisepithelial–mesenchymal transformationCXCR4neutrophilsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5703, p 5703 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CTNND1 bone metastasis epithelial–mesenchymal transformation CXCR4 neutrophils Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	CTNND1 bone metastasis epithelial–mesenchymal transformation CXCR4 neutrophils Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Qun Lin Xiaolin Fang Gehao Liang Qing Luo Yinghuan Cen Yu Shi Shijie Jia Juanmei Li Wenqian Yang Andrew J. Sanders Chang Gong Wenguo Jiang Silencing CTNND1 Mediates Triple-Negative Breast Cancer Bone Metastasis via Upregulating CXCR4/CXCL12 Axis and Neutrophils Infiltration in Bone
description	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.
format	article
author	Qun Lin Xiaolin Fang Gehao Liang Qing Luo Yinghuan Cen Yu Shi Shijie Jia Juanmei Li Wenqian Yang Andrew J. Sanders Chang Gong Wenguo Jiang
author_facet	Qun Lin Xiaolin Fang Gehao Liang Qing Luo Yinghuan Cen Yu Shi Shijie Jia Juanmei Li Wenqian Yang Andrew J. Sanders Chang Gong Wenguo Jiang
author_sort	Qun Lin
title	Silencing CTNND1 Mediates Triple-Negative Breast Cancer Bone Metastasis via Upregulating CXCR4/CXCL12 Axis and Neutrophils Infiltration in Bone
title_short	Silencing CTNND1 Mediates Triple-Negative Breast Cancer Bone Metastasis via Upregulating CXCR4/CXCL12 Axis and Neutrophils Infiltration in Bone
title_full	Silencing CTNND1 Mediates Triple-Negative Breast Cancer Bone Metastasis via Upregulating CXCR4/CXCL12 Axis and Neutrophils Infiltration in Bone
title_fullStr	Silencing CTNND1 Mediates Triple-Negative Breast Cancer Bone Metastasis via Upregulating CXCR4/CXCL12 Axis and Neutrophils Infiltration in Bone
title_full_unstemmed	Silencing CTNND1 Mediates Triple-Negative Breast Cancer Bone Metastasis via Upregulating CXCR4/CXCL12 Axis and Neutrophils Infiltration in Bone
title_sort	silencing ctnnd1 mediates triple-negative breast cancer bone metastasis via upregulating cxcr4/cxcl12 axis and neutrophils infiltration in bone
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5edc4f6d7c7948a9acf4e1bee4bdf1f2
work_keys_str_mv	AT qunlin silencingctnnd1mediatestriplenegativebreastcancerbonemetastasisviaupregulatingcxcr4cxcl12axisandneutrophilsinfiltrationinbone AT xiaolinfang silencingctnnd1mediatestriplenegativebreastcancerbonemetastasisviaupregulatingcxcr4cxcl12axisandneutrophilsinfiltrationinbone AT gehaoliang silencingctnnd1mediatestriplenegativebreastcancerbonemetastasisviaupregulatingcxcr4cxcl12axisandneutrophilsinfiltrationinbone AT qingluo silencingctnnd1mediatestriplenegativebreastcancerbonemetastasisviaupregulatingcxcr4cxcl12axisandneutrophilsinfiltrationinbone AT yinghuancen silencingctnnd1mediatestriplenegativebreastcancerbonemetastasisviaupregulatingcxcr4cxcl12axisandneutrophilsinfiltrationinbone AT yushi silencingctnnd1mediatestriplenegativebreastcancerbonemetastasisviaupregulatingcxcr4cxcl12axisandneutrophilsinfiltrationinbone AT shijiejia silencingctnnd1mediatestriplenegativebreastcancerbonemetastasisviaupregulatingcxcr4cxcl12axisandneutrophilsinfiltrationinbone AT juanmeili silencingctnnd1mediatestriplenegativebreastcancerbonemetastasisviaupregulatingcxcr4cxcl12axisandneutrophilsinfiltrationinbone AT wenqianyang silencingctnnd1mediatestriplenegativebreastcancerbonemetastasisviaupregulatingcxcr4cxcl12axisandneutrophilsinfiltrationinbone AT andrewjsanders silencingctnnd1mediatestriplenegativebreastcancerbonemetastasisviaupregulatingcxcr4cxcl12axisandneutrophilsinfiltrationinbone AT changgong silencingctnnd1mediatestriplenegativebreastcancerbonemetastasisviaupregulatingcxcr4cxcl12axisandneutrophilsinfiltrationinbone AT wenguojiang silencingctnnd1mediatestriplenegativebreastcancerbonemetastasisviaupregulatingcxcr4cxcl12axisandneutrophilsinfiltrationinbone
_version_	1718412777009184768

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

Ejemplares similares