Upregulation of CXCR4 is essential for HER2-mediated tumor metastasis

Yan M. Li; Yong Pan; Yongkun Wei; Xiaoyun Cheng; Binhua P. Zhou; Ming Tan; Xiaoyan Zhou; Weiya Xia; Gabriel N. Hortobagyi; Dihua Yu; Mien Chie Hung

doi:10.1016/j.ccr.2004.09.027

Upregulation of CXCR4 is essential for HER2-mediated tumor metastasis

Yan M. Li
, Yong Pan
, Yongkun Wei
, Xiaoyun Cheng
, Binhua P. Zhou
, Ming Tan
, Xiaoyan Zhou
, Weiya Xia
, Gabriel N. Hortobagyi
, Dihua Yu
, Mien Chie Hung

Producción científica: Article › revisión exhaustiva

501 Citas (Scopus)

Resumen

The receptor tyrosine kinase HER2 enhances tumor metastasis; however, its role in homing to metastatic organs is poorly understood. The chemokine receptor CXCR4 has recently been shown to mediate the movement of malignant cancer cells to specific organs. Here, we show that HER2 enhances the expression of CXCR4, which is required for HER2-mediated invasion in vitro and lung metastasis in vivo. HER2 also inhibits ligand-induced CXCR4 degradation. Finally, a significant correlation between HER2 and CXCR4 expression was observed in human breast tumor tissues, and CXCR4 expression correlated with a poor overall survival rate in patients with breast cancer. These results provide a plausible mechanism for HER2-mediated breast tumor metastasis and establish a functional link between HER2 and CXCR4 signaling pathways.

Idioma original	English
Páginas (desde-hasta)	459-469
Número de páginas	11
Publicación	Cancer Cell
Volumen	6
N.º	5
DOI	https://doi.org/10.1016/j.ccr.2004.09.027
Estado	Published - nov 2004

Nota bibliográfica

Funding Information:
This work was supported by NIH RO1 grants CA058880 and CA109311, PO1 CA099031, and the National Breast Cancer Research Foundation (M.-C.H.); DAMD 17-02-1-0694 (G.N.H.); MDACC Cancer Center Supporting Grant (CA16672); and a predoctoral fellowship from the US Army Breast Cancer Research Program, grant DAMD 17-02-1-0454 (Y.M.L.). We would like to thank Dr. Nelson L. Michael for CXCR4 plasmid; Dr. Benovic for HA-CXCR4 and FLAG-ubiquitin constructs; Dr. Tony Pawson for wild-type and catalytically inactive AIP4 plasmids; Dr. Jeng C. Cheng, Dr. Stephanie A. Miller, and the Department of Scientific Publications at the University of Texas M.D. Anderson Cancer Center for editing the manuscript; Bill Spohn for help with microscopy setup and image processing; Jean Wang for statistical assistance; Dr. Chin-Hsing Chen for performing mice tail vein injections; and Chu-Li Weng for preparing animal tissue.

Financiación

This work was supported by NIH RO1 grants CA058880 and CA109311, PO1 CA099031, and the National Breast Cancer Research Foundation (M.-C.H.); DAMD 17-02-1-0694 (G.N.H.); MDACC Cancer Center Supporting Grant (CA16672); and a predoctoral fellowship from the US Army Breast Cancer Research Program, grant DAMD 17-02-1-0454 (Y.M.L.). We would like to thank Dr. Nelson L. Michael for CXCR4 plasmid; Dr. Benovic for HA-CXCR4 and FLAG-ubiquitin constructs; Dr. Tony Pawson for wild-type and catalytically inactive AIP4 plasmids; Dr. Jeng C. Cheng, Dr. Stephanie A. Miller, and the Department of Scientific Publications at the University of Texas M.D. Anderson Cancer Center for editing the manuscript; Bill Spohn for help with microscopy setup and image processing; Jean Wang for statistical assistance; Dr. Chin-Hsing Chen for performing mice tail vein injections; and Chu-Li Weng for preparing animal tissue.

Financiadores	Número del financiador
National Breast Cancer Research Foundation	CA16672, DAMD 17-02-1-0454, DAMD 17-02-1-0694
National Institutes of Health (NIH)	CA109311, PO1 CA099031
National Institutes of Health (NIH)
National Childhood Cancer Registry – National Cancer Institute	R01CA058880
National Childhood Cancer Registry – National Cancer Institute

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Good health and well being

ASJC Scopus subject areas

Oncology
Cancer Research

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title = "Upregulation of CXCR4 is essential for HER2-mediated tumor metastasis",

abstract = "The receptor tyrosine kinase HER2 enhances tumor metastasis; however, its role in homing to metastatic organs is poorly understood. The chemokine receptor CXCR4 has recently been shown to mediate the movement of malignant cancer cells to specific organs. Here, we show that HER2 enhances the expression of CXCR4, which is required for HER2-mediated invasion in vitro and lung metastasis in vivo. HER2 also inhibits ligand-induced CXCR4 degradation. Finally, a significant correlation between HER2 and CXCR4 expression was observed in human breast tumor tissues, and CXCR4 expression correlated with a poor overall survival rate in patients with breast cancer. These results provide a plausible mechanism for HER2-mediated breast tumor metastasis and establish a functional link between HER2 and CXCR4 signaling pathways.",

author = "Li, \{Yan M.\} and Yong Pan and Yongkun Wei and Xiaoyun Cheng and Zhou, \{Binhua P.\} and Ming Tan and Xiaoyan Zhou and Weiya Xia and Hortobagyi, \{Gabriel N.\} and Dihua Yu and Hung, \{Mien Chie\}",

note = "Funding Information: This work was supported by NIH RO1 grants CA058880 and CA109311, PO1 CA099031, and the National Breast Cancer Research Foundation (M.-C.H.); DAMD 17-02-1-0694 (G.N.H.); MDACC Cancer Center Supporting Grant (CA16672); and a predoctoral fellowship from the US Army Breast Cancer Research Program, grant DAMD 17-02-1-0454 (Y.M.L.). We would like to thank Dr. Nelson L. Michael for CXCR4 plasmid; Dr. Benovic for HA-CXCR4 and FLAG-ubiquitin constructs; Dr. Tony Pawson for wild-type and catalytically inactive AIP4 plasmids; Dr. Jeng C. Cheng, Dr. Stephanie A. Miller, and the Department of Scientific Publications at the University of Texas M.D. Anderson Cancer Center for editing the manuscript; Bill Spohn for help with microscopy setup and image processing; Jean Wang for statistical assistance; Dr. Chin-Hsing Chen for performing mice tail vein injections; and Chu-Li Weng for preparing animal tissue.",

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AU - Li, Yan M.

AU - Pan, Yong

AU - Wei, Yongkun

AU - Cheng, Xiaoyun

AU - Zhou, Binhua P.

AU - Tan, Ming

AU - Zhou, Xiaoyan

AU - Xia, Weiya

AU - Hortobagyi, Gabriel N.

AU - Yu, Dihua

AU - Hung, Mien Chie

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PY - 2004/11

Y1 - 2004/11

N2 - The receptor tyrosine kinase HER2 enhances tumor metastasis; however, its role in homing to metastatic organs is poorly understood. The chemokine receptor CXCR4 has recently been shown to mediate the movement of malignant cancer cells to specific organs. Here, we show that HER2 enhances the expression of CXCR4, which is required for HER2-mediated invasion in vitro and lung metastasis in vivo. HER2 also inhibits ligand-induced CXCR4 degradation. Finally, a significant correlation between HER2 and CXCR4 expression was observed in human breast tumor tissues, and CXCR4 expression correlated with a poor overall survival rate in patients with breast cancer. These results provide a plausible mechanism for HER2-mediated breast tumor metastasis and establish a functional link between HER2 and CXCR4 signaling pathways.

AB - The receptor tyrosine kinase HER2 enhances tumor metastasis; however, its role in homing to metastatic organs is poorly understood. The chemokine receptor CXCR4 has recently been shown to mediate the movement of malignant cancer cells to specific organs. Here, we show that HER2 enhances the expression of CXCR4, which is required for HER2-mediated invasion in vitro and lung metastasis in vivo. HER2 also inhibits ligand-induced CXCR4 degradation. Finally, a significant correlation between HER2 and CXCR4 expression was observed in human breast tumor tissues, and CXCR4 expression correlated with a poor overall survival rate in patients with breast cancer. These results provide a plausible mechanism for HER2-mediated breast tumor metastasis and establish a functional link between HER2 and CXCR4 signaling pathways.

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Upregulation of CXCR4 is essential for HER2-mediated tumor metastasis

Resumen

Nota bibliográfica

Financiación

ODS de las Naciones Unidas

ASJC Scopus subject areas

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