ELP3,the catalytic subunit of the Elongator complex,is an acetyltransferase and associated with tumor progression.However,the detail of ELP3 oncogenic function remains largely unclear.Here,we found that ELP3 stabilizes c-Myc to promote tumorigenesis in an acetyltransferase-independent manner.Mechanistically,ELP3 competes with the E3-ligase FBXW7βfor c-Myc binding,resulting in the inhibition of FBXW7β-mediated ubiquitination and proteasomal degradation of c-Myc.ELP3 knockdown diminishes glycolysis and glutaminolysis and dramatically retards cell proliferation and xenograft growth by downregulating c-Myc,and such effects are rescued by the reconstitution of c-Myc expression.Moreover,ELP3 and c-Myc were found overexpressed with a positive correlation in colorectal cancer and hepatocellular carcinoma.Taken together,we elucidate a new function of ELP3 in promoting tumorigenesis by stabilizing c-Myc,suggesting that inhibition of ELP3 is a potential strategy for treating c-Myc-driven carcinomas.
Cell migration is a finely tuned biological process that often involves epithelial-mesenchymal transition(EMT).EMT is typically characterized by the upregulation of mesenchymal markers such as Snail1.This process has been shown to be of critical importance to normal developmental processes,including neural crest migration and invasion.Interestingly,similar mechanisms are utilized in disease processes,such as tumor metastasis and migration.Notably,EMT and EMT-like processes confer tumor cells with the ability to migrate,invade,and adopt stem cell-like properties that largely account for immunosuppression and tumor recurrence.Therefore,identifying sensitive EMT markers may contribute to cancer prognosis and diagnosis in many facets.Previously,we showed that Elp3 plays an essential role during neural crest migration by stabilizing Snail1.In the current study,we further elucidate the molecular mechanism underlying colorectal cancer migration.We found that mElp3 exerted an identical function to xElp3 in modulating neural crest migration,and both HAT and SAM domains are imperative during this migratory process.Interestingly,overexpression of mElp3 in SW480 cells promoted cell migration and invasion,and we further showed that Elp3 stabilized Snail1 requiring integrity of both SAM and HAT domains.Our findings warrant further exploration of the specific target of Elp3 in cancer cells.
Autophagy is responsible for maintaining fundamental cellular homeostasis and is,therefore,essential for diverse development processes.This study reported that PoElp3,the putative catalytic subunit of Elongator complex,is involved in the maintenance of autophagy homeostasis to facilitate asexual development and pathogenicity in the rice blast fungus Pyricularia oryzae.It was found that the ΔPoelp3 strains were defective in vegetative growth,conidiation,stress response,and pathogenicity.The mutants exhibited hyper-activated autophagy in the vegetative hyphae under both nutrient-rich and nutrient-deficient conditions.The hyper-activation of autophagy possibly suppressed the production of vegetative hyphae in the ΔPoelp3 strains.Moreover,the ΔPoelp3 strains were found to be more sensitive to rapamycin during vegetative-and invasive-hyphal growth but have no effect on Target-of-Rapamycin(TOR)signaling inhibition.Taken together,these results demonstrated that PoElp3 is involved in asexual development and pathogenicity by regulating autophagy in the rice blast fungus.
