Gain Fat-Lose Metastasis: Converting Invasive Breast Cancer Cells into Adipocytes Inhibits Cancer Metastasis
Gain Fat-Lose Metastasis: Converting Invasive Breast Cancer Cells into Adipocytes Inhibits Cancer Metastasis
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DOI：
10.1016/j.ccell.2018.12.002
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发表时间：
2019-01-14
期刊：
影响因子：
50.3
通讯作者：
Christofori, Gerhard
中科院分区：
文献类型：
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作者：
Ishay-Ronen, Dana;Diepenbruck, Maren;Christofori, Gerhard
癌细胞的可塑性促进了治疗抗性的产生和恶性进展。去分化过程，比如上皮 - 间质转化（EMT），已知会增强细胞的可塑性。在此，我们证明可以通过迫使EMT衍生的乳腺癌细胞转分化为有丝分裂后且具有功能的脂肪细胞，从而在治疗上利用癌细胞的可塑性。对这种转分化背后分子通路的描述，促使在体内多种小鼠和人类乳腺癌小鼠模型中采用MEK抑制剂和抗糖尿病药物罗格列酮进行联合治疗。这种联合治疗促使侵袭性和扩散性癌细胞转化为有丝分裂后脂肪细胞，从而抑制原发性肿瘤的侵袭和转移形成。
Cancer cell plasticity facilitates the development of therapy resistance and malignant progression. De-differentiation processes, such as an epithelial-mesenchymal transition (EMT), are known to enhance cellular plasticity. Here, we demonstrate that cancer cell plasticity can be exploited therapeutically by forcing the trans-differentiation of EMT-derived breast cancer cells into post-mitotic and functional adipocytes. Delineation of the molecular pathways underlying such trans-differentiation has motivated a combination therapy with MEK inhibitors and the anti-diabetic drug Rosiglitazone in various mouse models of murine and human breast cancer in vivo. This combination therapy provokes the conversion of invasive and disseminating cancer cells into post-mitotic adipocytes leading to the repression of primary tumor invasion and metastasis formation.