Journal
ONCOGENE
Volume 38, Issue 23, Pages 4637-4654Publisher
SPRINGERNATURE
DOI: 10.1038/s41388-019-0747-0
Keywords
-
Funding
- National Key R&D Program of China [2017YFC1105000]
- National Natural Science Foundation of China [81702398]
- Natural Science Foundation of Guangdong Province of China [2016A020215232]
Ask authors/readers for more resources
Chemotherapy is the preferred treatment for advanced stage gastric cancer (GC) patients and chemotherapy resistance is the major obstacle to effective cancer therapy. Increasing evidence suggests that mesenchymal stem cells (MSCs) make important contributions to development of drug resistance. However, the underlying mechanism remains elusive. In this study, we discovered that abundant MSCs in tumor tissues predicted a poor prognosis in GC patients. MSCs promoted stemness and chemoresistance in GC cells through fatty acid oxidation (FAO) in vitro and in vivo. Mechanically, transforming growth factor beta 1 (TGF-beta 1) secretion by MSCs activated SMAD2/3 through TGF-beta receptors and induced long non-coding RNA (lncRNA) MACC1-AS1 expression in GC cells, which promoted FAO-dependent stemness and chemoresistance through antagonizing miR-145-5p. Moreover, pharmacologic inhibition of FAO with etomoxir (ETX) attenuated MSC-induced FOLFOX regiment resistance in vivo. These results suggest that FAO plays an important role in MSC-mediated stemness and chemotherapy resistance in GC and FAO inhibitors in combination with chemotherapeutic drugs present as a promising strategy to overcome chemoresistance.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available