title: Adipocyte activation of cancer stem cell signaling in breast cancer.
abstract: Signaling within the tumor microenvironment has a critical role in cancer initiation and progression. Adipocytes, one of the major components of the breast microenvironment, have been shown to provide pro-tumorigenic signals that promote cancer cell proliferation and invasiveness in vitro and tumorigenicity in vivo. Adipocyte secreted factors such as leptin and interleukin-6 (IL-6) have a paracrine effect on breast cancer cells. In adipocyte-adjacent breast cancer cells, the leptin and IL-6 signaling pathways activate janus kinase 2/signal transducer and activator of transcription 5, promoting the epithelial-mesenchymal transition, and upregulating stemness regulators such as Notch, Wnt and the Sex determining region Y-box 2/octamer binding transcription factor 4/Nanog signaling axis. In this review we will summarize the major signaling pathways that regulate cancer stem cells in breast cancer and describe the effects that adipocyte secreted IL-6 and leptin have on breast cancer stem cell signaling. Finally we will introduce a new potential treatment paradigm of inhibiting the adipocyte-breast cancer cell signaling via targeting the IL-6 or leptin pathways.
authors.affiliation: Benjamin Wolfson, Gabriel Eades, Qun Zhou, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wolfson
authors.affiliation: Benjamin Wolfson, Gabriel Eades, Qun Zhou, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Eades
authors.affiliation: Benjamin Wolfson, Gabriel Eades, Qun Zhou, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Qun
authors.initials: Q
authors.lastname: Zhou
keywords: Adipocyte; Breast cancer; Cancer stem cells; Epithelial-mesenchymal transition; Interleukin-6; Leptin; Microenvironment