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Rios Garcia, M. ; Steinbauer, B.* ; Srivastava, K.* ; Singhal, M.* ; Mattijssen, F. ; Maida, A. ; Christian, S.* ; Hess-Stumpp, H.* ; Augustin, H.G.* ; Müller-Decker, K.* ; Nawroth, P.P. ; Herzig, S. ; Berriel Diaz, M.

Acetyl-CoA carboxylase 1-dependent protein acetylation controls breast cancer metastasis and recurrence.

Cell Metab. 26, 1–14.e1–e5 (2017)
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Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Emt ; Acetyl-coa ; Acetylation ; Breast Cancer ; Leptin ; Metastasis ; Pacc; Fatty-acid Synthesis; Mesenchymal Transition; Molecular-mechanisms; Signaling Pathway; Cell-survival; Energy Stress; Metabolism; Leptin; Inhibition; Growth
ISSN (print) / ISBN 1550-4131
e-ISSN 1932-7420
Journal Cell Metabolism
Quellenangaben Volume: 26, Issue: 6, Pages: 1–14.e1–e5 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Cambridge
Reviewing status Peer reviewed