Authors:
Shanyan Bian, Yingwei Guo, […], and Jiancong Huang +3 (View all authors)
Abstract
As a serious malignancy of the head and neck region, laryngeal cancer (LC) exhibits active glycolysis that produces lactate, a metabolite capable of inducing protein lactylation. However, the role of lactate-induced modifications in LC progression remains poorly understood. Although ALYREF has been identified as an oncogenic driver in several cancers, its function in LC has not yet been investigated.
Malignant cell behaviors were assessed using Cell Counting Kit-8, EdU staining, glucose uptake, lactate production, and extracellular acidification rate (ECAR) assays. The experimental methodology also included quantitative real-time PCR, western blot, and xenograft tumor models.
Data demonstrated that ALYREF is markedly overexpressed in LC and holds potential diagnostic value. Knockdown of ALYREF impaired both proliferation and glycolytic capacity in LC cells. Mechanistically, increased lactate levels promoted lactylation of ALYREF at the K171 site, which in turn enhanced ALYREF expression. Elevated lactate concentrations rescued the suppression of oncogenic phenotypes and glycolysis induced by ALYREF reduction. Furthermore, in vivo experiments confirmed that ALYREF silencing inhibited tumor growth.
Our findings indicate that ALYREF promotes tumor progression by enhancing glycolysis. Glycolysis-derived lactate stabilizes the ALYREF protein via lactylation at K171, establishing a positive feedback loop that drives LC malignancy. Silencing ALYREF suppresses tumor growth, underscoring its potential as a therapeutic target in LC.
Malignant cell behaviors were assessed using Cell Counting Kit-8, EdU staining, glucose uptake, lactate production, and extracellular acidification rate (ECAR) assays. The experimental methodology also included quantitative real-time PCR, western blot, and xenograft tumor models.
Data demonstrated that ALYREF is markedly overexpressed in LC and holds potential diagnostic value. Knockdown of ALYREF impaired both proliferation and glycolytic capacity in LC cells. Mechanistically, increased lactate levels promoted lactylation of ALYREF at the K171 site, which in turn enhanced ALYREF expression. Elevated lactate concentrations rescued the suppression of oncogenic phenotypes and glycolysis induced by ALYREF reduction. Furthermore, in vivo experiments confirmed that ALYREF silencing inhibited tumor growth.
Our findings indicate that ALYREF promotes tumor progression by enhancing glycolysis. Glycolysis-derived lactate stabilizes the ALYREF protein via lactylation at K171, establishing a positive feedback loop that drives LC malignancy. Silencing ALYREF suppresses tumor growth, underscoring its potential as a therapeutic target in LC.