This review describes the multifaceted effects of adiponectin on breast cancer cell signalling, tumour metabolism, and microenvironment. It is largely documented that low adiponectin levels are associated with an increased risk of breast cancer. However, it needs to be still clarified what are the extents of the decrease of local/intra‐tumoural adiponectin concentrations, which promote breast tumour malignancy. Most of the anti‐proliferative and pro‐apoptotic effects induced by adiponectin have been obtained in breast cancer cells not expressing estrogen receptor alpha (ERα). Here, we will highlight recent findings demonstrating the mechanistic effects through which adiponectin is able to fuel genomic and non‐genomic estrogen signalling, inhibiting LKB1/AMPK/mTOR/S6K pathway and switching energy balance. Therefore, it emerges that the reduced adiponectin levels in patients with obesity work to sustain tumour growth and progression in ERα‐positive breast cancer cells. All this may contribute to remove the misleading paradigm that adiponectin univocally inhibits breast cancer cell growth and progression independently on ERα status. The latter concept, here clearly provided by pre‐clinical studies, may have translational relevance adopting adiponectin as a potential therapeutic tool. Indeed, the interfering role of ERα on adiponectin action addresses how a separate assessment of adiponectin treatment needs to be considered in novel therapeutic strategies for ERα‐positive and ERα‐negative breast cancer.

中文翻译：

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对脂联素在乳腺癌中的作用的新见解：ERα 表达介导的机制效应的证据。

本综述描述了脂联素对乳腺癌细胞信号、肿瘤代谢和微环境的多方面影响。大量文献记载，低脂联素水平与乳腺癌风险增加有关。然而，仍需要澄清促进乳腺肿瘤恶性的局部/肿瘤内脂联素浓度降低的程度。大多数由脂联素诱导的抗增殖和促凋亡作用是在不表达雌激素受体α (ERα) 的乳腺癌细胞中获得的。在这里，我们将重点介绍最近的发现，证明脂联素能够促进基因组和非基因组雌激素信号传导、抑制 LKB1/AMPK/mTOR/S6K 通路和转换能量平衡的机制效应。所以，结果表明，肥胖患者体内脂联素水平降低有助于维持 ERα 阳性乳腺癌细胞的肿瘤生长和进展。所有这些可能有助于消除脂联素单方面抑制乳腺癌细胞生长和进展的误导性范式，独立于 ERα 状态。后一个概念由临床前研究明确提供，采用脂联素作为潜在的治疗工具可能具有转化相关性。事实上，ERα 对脂联素作用的干扰作用解决了如何在 ERα 阳性和 ERα 阴性乳腺癌的新治疗策略中考虑单独评估脂联素治疗。所有这些可能有助于消除脂联素单方面抑制乳腺癌细胞生长和进展的误导性范式，独立于 ERα 状态。后一个概念由临床前研究明确提供，采用脂联素作为潜在的治疗工具可能具有转化相关性。事实上，ERα 对脂联素作用的干扰作用解决了如何在 ERα 阳性和 ERα 阴性乳腺癌的新治疗策略中考虑单独评估脂联素治疗。所有这些可能有助于消除脂联素单方面抑制乳腺癌细胞生长和进展的误导性范式，独立于 ERα 状态。后一个概念由临床前研究明确提供，采用脂联素作为潜在的治疗工具可能具有转化相关性。事实上，ERα 对脂联素作用的干扰作用解决了如何在 ERα 阳性和 ERα 阴性乳腺癌的新治疗策略中考虑单独评估脂联素治疗。