转移
乳腺癌
癌症研究
转移性乳腺癌
癌症
磷酸化
内科学
原发性肿瘤
生物
医学
肿瘤科
乙酰辅酶A羧化酶
丙酮酸羧化酶
酶
细胞生物学
生物化学
作者
Marcos Ríos García,Brigitte Steinbauer,Kshitij Srivastava,Mahak Singhal,Frits Mattijssen,Adriano Maida,Sven Christian,Holger Hess‐Stumpp,Hellmut G. Augustin,Karin Müller‐Decker,Peter P. Nawroth,Stephan Herzig,Mauricio Berriel Díaz
出处
期刊:Cell Metabolism
[Elsevier]
日期:2017-12-01
卷期号:26 (6): 842-855.e5
被引量:183
标识
DOI:10.1016/j.cmet.2017.09.018
摘要
Breast tumor recurrence and metastasis represent the main causes of cancer-related death in women, and treatments are still lacking. Here, we define the lipogenic enzyme acetyl-CoA carboxylase (ACC) 1 as a key player in breast cancer metastasis. ACC1 phosphorylation was increased in invading cells both in murine and human breast cancer, serving as a point of convergence for leptin and transforming growth factor (TGF) β signaling. ACC1 phosphorylation was mediated by TGFβ-activated kinase (TAK) 1, and ACC1 inhibition was indispensable for the elevation of cellular acetyl-CoA, the subsequent increase in Smad2 transcription factor acetylation and activation, and ultimately epithelial-mesenchymal transition and metastasis induction. ACC1 deficiency worsened tumor recurrence upon primary tumor resection in mice, and ACC1 phosphorylation levels correlated with metastatic potential in breast and lung cancer patients. Given the demonstrated effectiveness of anti-leptin receptor antibody treatment in halting ACC1-dependent tumor invasiveness, our work defines a “metabolocentric” approach in metastatic breast cancer therapy.
科研通智能强力驱动
Strongly Powered by AbleSci AI