| Autor: |
Ana P. Gomes, Didem Ilter, Vivien Low, Stanislav Drapela, Tanya Schild, Edouard Mullarky, Julie Han, Ilaria Elia, Dorien Broekaert, Adam Rosenzweig, Michal Nagiec, Joana B. Nunes, Bethany E. Schaffer, Anders P. Mutvei, John M. Asara, Lewis C. Cantley, Sarah-Maria Fendt, John Blenis |
| Jazyk: |
angličtina |
| Předmět: |
|
| Zdroj: |
Nature Metabolism |
| ISSN: |
2522-5812 |
| DOI: |
10.1038/s42255-022-00553-5 |
| Popis: |
The alteration of metabolic pathways is a critical strategy for cancer cells to attain the traits necessary for metastasis in disease progression. Here, we find that dysregulation of propionate metabolism produces a pro-aggressive signature in breast and lung cancer cells, increasing their metastatic potential. This occurs through the downregulation of methylmalonyl coenzyme A epimerase (MCEE), mediated by an extracellular signal-regulated kinase 2-driven transcription factor Sp1/early growth response protein 1 transcriptional switch driven by metastatic signalling at its promoter level. The loss of MCEE results in reduced propionate-driven anaplerotic flux and intracellular and intratumoral accumulation of methylmalonic acid, a by-product of propionate metabolism that promotes cancer cell invasiveness. Altogether, we present a previously uncharacterized dysregulation of propionate metabolism as an important contributor to cancer and a valuable potential target in the therapeutic treatment of metastatic carcinomas. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
