Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration.
Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration.
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DOI：
10.1186/s40170-016-0163-7
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发表时间：
2017
影响因子：
5.9
通讯作者：
Hoy AJ
中科院分区：
文献类型：
--
作者：
Balaban S;Shearer RF;Lee LS;van Geldermalsen M;Schreuder M;Shtein HC;Cairns R;Thomas KC;Fazakerley DJ;Grewal T;Holst J;Saunders DN;Hoy AJ
肥胖与乳腺癌复发增加和生存率降低有关。脂肪细胞是乳腺组织的重要组成部分，但对脂肪细胞提供代谢底物以支持乳腺癌进展的作用知之甚少。在这里，我们表明，乳腺癌细胞与脂肪细胞共培养发现，癌细胞刺激脂肪细胞三酰甘油的消耗。脂肪细胞来源的游离脂肪酸被转移到乳腺癌细胞，通过增加CPT1A和电子传输链复合体蛋白水平来推动脂肪酸代谢，从而促进增殖和迁移。值得注意的是，随着癌细胞增殖和迁移的刺激增加，“肥胖”脂肪细胞向乳腺癌细胞的脂肪酸转移增加。这种脂肪细胞刺激的乳腺癌细胞增殖依赖于脂解过程，因为HSL/ATGL基因敲除会减弱癌细胞的反应。这些发现突出了脂肪细胞脂肪分解在为乳腺癌细胞提供代谢底物从而支持癌症进展中的一个新的和潜在的重要作用。本文的在线版本(doi：10.1186/s40170160.163-7)包含补充材料，授权用户可以使用。
Obesity is associated with increased recurrence and reduced survival of breast cancer. Adipocytes constitute a significant component of breast tissue, yet their role in provisioning metabolic substrates to support breast cancer progression is poorly understood. Here, we show that co-culture of breast cancer cells with adipocytes revealed cancer cell-stimulated depletion of adipocyte triacylglycerol. Adipocyte-derived free fatty acids were transferred to breast cancer cells, driving fatty acid metabolism via increased CPT1A and electron transport chain complex protein levels, resulting in increased proliferation and migration. Notably, fatty acid transfer to breast cancer cells was enhanced from “obese” adipocytes, concomitant with increased stimulation of cancer cell proliferation and migration. This adipocyte-stimulated breast cancer cell proliferation was dependent on lipolytic processes since HSL/ATGL knockdown attenuated cancer cell responses. These findings highlight a novel and potentially important role for adipocyte lipolysis in the provision of metabolic substrates to breast cancer cells, thereby supporting cancer progression. The online version of this article (doi:10.1186/s40170-016-0163-7) contains supplementary material, which is available to authorized users.