Metabolic adaptations play a key role in fueling tumor growth. However, less is known regarding the metabolic changes that promote cancer progression to metastatic disease. Herein, we reveal that breast cancer cells that preferentially metastasize to the lung or bone display relatively high expression of PGC-1α compared with those that metastasize to the liver. PGC-1α promotes breast cancer cell migration and invasionin vitroand augments lung metastasisin vivo. Pro-metastatic capabilities of PGC-1α are linked to enhanced global bioenergetic capacity, facilitating the ability to cope with bioenergetic disruptors like biguanides. Indeed, biguanides fail to mitigate the PGC-1α-dependent lung metastatic phenotype and PGC-1α confers resistance to stepwise increases in metformin concentration. Overall, our results reveal that PGC-1α stimulates bioenergetic potential, which promotes breast cancer metastasis and facilitates adaptation to metabolic drugs.

中文翻译：

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PGC-1α促进乳腺癌转移并赋予生物能抵抗代谢药物的灵活性。

代谢适应在促进肿瘤生长中起关键作用。然而，关于促进癌症发展成转移性疾病的代谢变化知之甚少。在此，我们揭示了优先转移至肺或骨的乳腺癌细胞与转移至肝脏的乳腺癌细胞相比，PGC-1α的表达相对较高。PGC-1α在体外促进乳腺癌细胞的迁移和侵袭，并在体内增强肺转移。PGC-1α的转移前能力与增强的全球生物能能力有关，从而促进了应对双胍等生物能破坏者的能力。实际上，双胍类药物不能减轻PGC-1α依赖性的肺转移表型，并且PGC-1α赋予对二甲双胍浓度逐步增加的抵抗力。全面的，