PDF(Pubmed)
Abstract：
BACKGROUND: Breast cancer manifests as a heterogeneous pathology marked by complex metabolic reprogramming essential to satisfy its energy demands. Oncogenic signals boost the metabolism, modifying fatty acid synthesis and glucose use from the onset to progression and therapy resistant-forms. However, the exact contribution of metabolic dependencies during tumor evolution remains unclear.
METHODS: In this study, we elucidate the connection between FASN and LDHA, pivotal metabolic genes, and their correlation with tumor grade and therapy response using datasets from public repositories. Subsequently, we evaluated the metabolic and proliferative functions upon FASN and LDHA inhibition in breast cancer models. Lastly, we integrated metabolomic and lipidomic analysis to define the contributions of metabolites, lipids, and precursors to the metabolic phenotypes.
RESULTS: Collectively, our findings indicate metabolic shifts during breast cancer progression, unvealling two distinct functional energy phenotypes associated with aggressiveness and therapy response. Specifically, FASN exhibits reduced expression in advance-grade tumors and therapy-resistant forms, whereas LDHA demonstrates higher expression. Additionally, the biological and metabolic impact of blocking the enzymatic activity of FASN and LDHA was correlated with resistant conditions.
CONCLUSIONS: These observations emphasize the intrinsic metabolic heterogeneity within breast cancer, thereby highlighting the relevance of metabolic interventions in the field of precision medicine.
METHODS: In this study, we elucidate the connection between FASN and LDHA, pivotal metabolic genes, and their correlation with tumor grade and therapy response using datasets from public repositories. Subsequently, we evaluated the metabolic and proliferative functions upon FASN and LDHA inhibition in breast cancer models. Lastly, we integrated metabolomic and lipidomic analysis to define the contributions of metabolites, lipids, and precursors to the metabolic phenotypes.
RESULTS: Collectively, our findings indicate metabolic shifts during breast cancer progression, unvealling two distinct functional energy phenotypes associated with aggressiveness and therapy response. Specifically, FASN exhibits reduced expression in advance-grade tumors and therapy-resistant forms, whereas LDHA demonstrates higher expression. Additionally, the biological and metabolic impact of blocking the enzymatic activity of FASN and LDHA was correlated with resistant conditions.
CONCLUSIONS: These observations emphasize the intrinsic metabolic heterogeneity within breast cancer, thereby highlighting the relevance of metabolic interventions in the field of precision medicine.
摘要：
背景：乳腺癌表现为一种异质性病理，其特征是复杂的代谢重编程对于满足其能量需求至关重要。致癌信号促进新陈代谢，从发病到进展和治疗抗性形式改变脂肪酸合成和葡萄糖使用。然而,代谢依赖性在肿瘤进化过程中的确切作用尚不清楚.
方法：在本研究中，我们阐明了FASN和LDHA之间的联系，关键的代谢基因，使用来自公共存储库的数据集，以及它们与肿瘤分级和治疗反应的相关性。随后，我们评估了乳腺癌模型中FASN和LDHA抑制后的代谢和增殖功能。最后,我们整合了代谢组学和脂质组学分析来定义代谢物的贡献，脂质，和代谢表型的前体。
结果：总的来说，我们的发现表明乳腺癌进展过程中的代谢变化，揭示了与攻击性和治疗反应相关的两种不同的功能能量表型。具体来说,FASN在高级肿瘤和治疗耐药形式中表现出降低的表达，而LDHA表现出更高的表达。此外,阻断FASN和LDHA酶活性的生物学和代谢影响与抗性条件相关。
结论：这些观察强调了乳腺癌的内在代谢异质性，从而突出了代谢干预在精准医学领域的相关性。
方法：在本研究中，我们阐明了FASN和LDHA之间的联系，关键的代谢基因，使用来自公共存储库的数据集，以及它们与肿瘤分级和治疗反应的相关性。随后，我们评估了乳腺癌模型中FASN和LDHA抑制后的代谢和增殖功能。最后,我们整合了代谢组学和脂质组学分析来定义代谢物的贡献，脂质，和代谢表型的前体。
结果：总的来说，我们的发现表明乳腺癌进展过程中的代谢变化，揭示了与攻击性和治疗反应相关的两种不同的功能能量表型。具体来说,FASN在高级肿瘤和治疗耐药形式中表现出降低的表达，而LDHA表现出更高的表达。此外,阻断FASN和LDHA酶活性的生物学和代谢影响与抗性条件相关。
结论：这些观察强调了乳腺癌的内在代谢异质性，从而突出了代谢干预在精准医学领域的相关性。
