Research Papers:

Acetyl-CoA carboxylase inhibitors attenuate WNT and Hedgehog signaling and suppress pancreatic tumor growth

Elissaveta Petrova _, Arne Scholz, Juliane Paul, Andrea Sturz, Katja Haike, Franziska Siegel, Dominik Mumberg and Ningshu Liu

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2017; 8:48660-48670. https://doi.org/10.18632/oncotarget.12650

Metrics: PDF 3242 views  |   HTML 3887 views  |   ?  


Elissaveta Petrova1,2, Arne Scholz1, Juliane Paul1, Andrea Sturz1, Katja Haike1, Franziska Siegel1, Dominik Mumberg1 and Ningshu Liu1

1 Bayer AG, Drug Discovery, Berlin, Germany

2 Current address: Merck KGaA, Darmstadt, Germany

Correspondence to:

Elissaveta Petrova, email:

Ningshu Liu, email:

Keywords: ACC, WNT, Hedgehog, lipidation, PDAC

Received: September 30, 2016 Accepted: October 07, 2016 Published: October 13, 2016


Acetyl-CoA carboxylase (ACC) is the rate-limiting enzyme in de novo fatty acid synthesis, and its ACC1 isoform is overexpressed in pancreatic and various other cancers. The activity of many oncogenic signaling molecules, including WNT and Hedgehog (HH), is post-translationally modified by lipidation. Here, we report that inhibition of ACC by a small molecule inhibitor, BAY ACC002, blocked WNT3A lipidation, secretion, and signaling. In pancreatic cancer cells, where WNT and HH are key oncogenic drivers, ACC inhibition simultaneously suppressed WNT and HH signaling, and led to anti-proliferative effects. Treatment with ACC inhibitors blocked tumor growth and converted the poorly differentiated histological phenotype to epithelial phenotype in multiple cell line-based and patient-derived pancreatic cancer xenograft models. Together, our data highlight the potential utility of ACC inhibitors for pancreatic cancer treatment, and provide novel insight into the link between upregulated de novo fatty acid synthesis in cancer cells, protein lipidation, and oncogenic signaling.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 12650