Plexin-B3 expression stimulates MET signaling, breast cancer stem cell specification, and lung metastasis

Qiaozhu Zuo; Yongkang Yang; Yajing Lyu; Chen Yang; Chelsey Chen; Shaima Salman; Tina Yi-Ting Huang; Elizabeth E. Wicks; Walter Jackson, III; Emmanuel Datan; Wenxin Qin; Gregg L. Semenza

Cell Reports (Mar 2023)

Plexin-B3 expression stimulates MET signaling, breast cancer stem cell specification, and lung metastasis

Qiaozhu Zuo,
Yongkang Yang,
Yajing Lyu,
Chen Yang,
Chelsey Chen,
Shaima Salman,
Tina Yi-Ting Huang,
Elizabeth E. Wicks,
Walter Jackson, III,
Emmanuel Datan,
Wenxin Qin,
Gregg L. Semenza

Affiliations

Qiaozhu Zuo: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
Yongkang Yang: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21205, USA
Yajing Lyu: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Chen Yang: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
Chelsey Chen: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Shaima Salman: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Tina Yi-Ting Huang: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Elizabeth E. Wicks: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Walter Jackson, III: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Emmanuel Datan: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Wenxin Qin: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
Gregg L. Semenza: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21205, USA; Departments of Biological Chemistry, Medicine, Pediatrics, and Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Corresponding author

Journal volume & issue: Vol. 42, no. 3
p. 112164

Abstract

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Summary: Intratumoral hypoxia is a microenvironmental feature that promotes breast cancer progression and is associated with cancer mortality. Plexin B3 (PLXNB3) is highly expressed in estrogen receptor-negative breast cancer, but the underlying mechanisms and consequences have not been thoroughly investigated. Here, we report that PLXNB3 expression is increased in response to hypoxia and that PLXNB3 is a direct target gene of hypoxia-inducible factor 1 (HIF-1) in human breast cancer cells. PLXNB3 expression is correlated with HIF-1α immunohistochemistry, breast cancer grade and stage, and patient mortality. Mechanistically, PLXNB3 is required for hypoxia-induced MET/SRC/focal adhesion kinase (FAK) and MET/SRC/STAT3/NANOG signaling as well as hypoxia-induced breast cancer cell migration, invasion, and cancer stem cell specification. PLXNB3 knockdown impairs tumor formation and lung metastasis in orthotopic breast cancer mouse models.

CP: Cancer

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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