Adipocyte activation of cancer stem cell signaling in breast cancer.
Adipocyte activation of cancer stem cell signaling in breast cancer.
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DOI：
10.4331/wjbc.v6.i2.39
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发表时间：
2015-05
期刊：
影响因子：
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通讯作者：
Benjamin Wolfson;Gabriel L Eades;Qun Zhou
中科院分区：
文献类型：
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作者：
Benjamin Wolfson;Gabriel L Eades;Qun Zhou
肿瘤微环境内的信号传导在癌症的发生和进展中发挥着关键作用。脂肪细胞是乳腺微环境的主要组成部分之一，已被证明可以提供促肿瘤信号，促进癌细胞增殖和体外侵袭性以及体内致瘤性。脂肪细胞分泌的因子如瘦素和白细胞介素6 (IL-6) 对乳腺癌细胞具有旁分泌作用。在脂肪细胞邻近的乳腺癌细胞中，瘦素和 IL-6 信号通路激活 janus 激酶 2/信号转导器和转录激活剂 5，促进上皮-间质转化，并上调干性调节因子，如 Notch、Wnt 和性别决定区 Y-box 2/八聚体结合转录因子 4/Nanog 信号轴。在这篇综述中，我们将总结调节乳腺癌干细胞的主要信号通路，并描述脂肪细胞分泌的 IL-6 和瘦素对乳腺癌干细胞信号传导的影响。最后，我们将介绍一种新的潜在治疗范例，通过靶向 IL-6 或瘦素途径来抑制脂肪细胞-乳腺癌细胞信号传导。
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.