ASCT2 palmitoylation regulated by JNK1-ZDHHC14 axis orchestrates glutamine metabolism and NSCLC progression - PubMed
3 hours ago
- #NSCLC
- #ASCT2
- #palmitoylation
- ASCT2 palmitoylation is regulated by the JNK1-ZDHHC14 axis, impacting glutamine metabolism and NSCLC progression.
- ZDHHC14 is identified as the key palmitoyltransferase for ASCT2 at Cys39 and Cys48, promoting its lysosomal degradation, while ABHD17B acts as a depalmitoylase to stabilize ASCT2.
- Glutamine deprivation activates JNK1, which phosphorylates ZDHHC14 at Thr440, leading to its degradation and increased ASCT2 stability.
- Combining JNK and ASCT2 inhibitors synergistically inhibits glutamine metabolism and tumor growth in vivo.
- The study reveals a phosphorylation-palmitoylation axis connecting JNK-mediated ASCT2 palmitoylation to glutamine metabolism, suggesting a therapeutic strategy for NSCLC.