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World J Biol Chem. May 26, 2015; 6(2): 39-47
Published online May 26, 2015. doi: 10.4331/wjbc.v6.i2.39
Adipocyte activation of cancer stem cell signaling in breast cancer
Benjamin Wolfson, Gabriel Eades, Qun Zhou
Benjamin Wolfson, Gabriel Eades, Qun Zhou, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, United States
Author contributions: Wolfson B wrote the manuscript and generated the figure; Eades G reviewed the manuscript; Zhou Q designed the aim of the review and reviewed the manuscript.
Conflict-of-interest: None.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Qun Zhou, MD, PhD, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 22 S Greene St, Baltimore, MD 21201, United States. qzhou@som.umaryland.edu
Telephone: +1-410-7061615 Fax: +1-410-7068297
Received: January 27, 2015
Peer-review started: January 28, 2015
First decision: March 6, 2015
Revised: March 18, 2015
Accepted: April 16, 2015
Article in press: April 20, 2015
Published online: May 26, 2015
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.

Keywords: Breast cancer, Interleukin-6, Cancer stem cells, Adipocyte, Microenvironment, Epithelial-mesenchymal transition, Leptin

Core tip: We discuss the relationship between adipocytes in the microenvironment and breast cancer cells. We emphasize the role of adipocyte-secreted leptin and interleukin-6 in inducing breast cancer cell epithelial-mesenchymal transition and activating stemness pathways. Finally we summarize possible microenvironmental therapeutic targets and the potential role of non-coding RNAs in adipocyte-breast cancer interactions.