ACSL3活化脂肪酸β氧化介导TGFβ1诱导的EMT和肿瘤转移分子机制研究

Energy metabolic reprogramming represents one of hallmarks of cancer. The specific metabolic pattern such as activation of fatty acid metabolism plays an important role in cancer invasion and metastasis. As a key regulator of lipid metabolism, the deregulation of Acyl-coenzyme A (CoA) synthetase longchain family member 3 (ACSL3) is closely associated with tumor malignant progression and poor prognosis..Taken ACSL3 as the pointcut, this project aims to reveal that ACSL3 promotes the activation of fatty acid oxidation (FAO), which leads to mitochondrial energy metabolic reprogramming, to mediate TGFβ1-induced epithelial-mesenchymal transition (EMT) and cancer metastasis. This research will further elucidate the correlation between mitochondrial metabolic reprogramming and cancer aggressive and metastatic phenotype. And it may provide new scope and key molecular targets for cancer targeted therapy.

能量代谢重编程是肿瘤的重要特征，肿瘤细胞特定的代谢重塑如脂肪酸代谢活化在肿瘤的侵袭转移进展中具有重要功能。长链脂酰辅酶A合成酶3 (ACSL3) 作为脂代谢的关键调节元件，其异常活化与多种肿瘤的恶性进展及预后不良相关。本项目以ACSL3为切入点，通过明确ACSL3活化脂肪酸β氧化（FAO），促进线粒体能量代谢重编程，介导TGFβ1诱导的肿瘤细胞EMT与转移的分子机制，将从一个新的视野阐释细胞线粒体能量代谢重塑与肿瘤侵袭转移表型的内在联系，为肿瘤的分子靶向治疗提供崭新的视角和新颖的分子靶点。

能量代谢重编程是肿瘤的重要特征，肿瘤细胞特定的代谢重塑如脂肪酸代谢活化在肿瘤的侵袭转移进展中具有重要功能。长链脂酰辅酶A合成酶3 (ACSL3) 作为脂代谢的关键调节元件，其异常活化与多种肿瘤的恶性进展及预后不良相关。本项目以ACSL3为切入点，初步明确了ACSL3活化脂肪酸β氧化（FAO），促进线粒体能量代谢重编程，介导TGFβ1诱导的肿瘤细胞EMT与转移的分子机制，将从一个新的视野阐释细胞线粒体能量代谢重塑与肿瘤侵袭转移表型的内在联系，为肿瘤的分子靶向治疗提供崭新的视角和新颖的分子靶点。