TY  - JOUR
AU  - Rios Garcia, Marcos
AU  - Steinbauer, Brigitte
AU  - Srivastava, Kshitij
AU  - Singhal, Mahak
AU  - Mattijssen, Frits
AU  - Maida, Adriano
AU  - Christian, Sven
AU  - Hess-Stumpp, Holger
AU  - Augustin, Hellmut
AU  - Müller-Decker, Karin
AU  - Nawroth, Peter P
AU  - Herzig, Stephan
AU  - Berriel Diaz, Mauricio
TI  - Acetyl-CoA Carboxylase 1-Dependent Protein Acetylation Controls Breast Cancer Metastasis and Recurrence.
JO  - Cell metabolism
VL  - 26
IS  - 6
SN  - 1550-4131
CY  - Amsterdam [u.a.]
PB  - Elsevier
M1  - DKFZ-2017-06238
SP  - 842 - 855.e5
PY  - 2017
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:29056512
DO  - DOI:10.1016/j.cmet.2017.09.018
UR  - https://inrepo02.dkfz.de/record/131606
ER  -