Journal
CELL DEATH & DISEASE
Volume 14, Issue 10, Pages -Publisher
SPRINGERNATURE
DOI: 10.1038/s41419-023-06208-x
Keywords
-
Categories
Ask authors/readers for more resources
SYVN1 E3 ubiquitin ligase post-translationally regulates the localization and function of MCT4, affecting metabolic reprogramming in tumor cells and predicting poor prognosis in patients with LUAD.
Tumour cells mainly generate energy from glycolysis, which is commonly coupled with lactate production even under normoxic conditions. As a critical lactate transporter, monocarboxylate transporter 4 (MCT4) is highly expressed in glycolytic tissues, such as muscles and tumours. Overexpression of MCT4 is associated with poor prognosis for patients with various tumours. However, how MCT4 function is post-translationally regulated remains largely unknown. Taking advantage of human lung adenocarcinoma (LUAD) cells, this study revealed that MCT4 can be polyubiquitylated in a nonproteolytic manner by SYVN1 E3 ubiquitin ligase. The polyubiquitylation facilitates the localization of MCT4 into the plasma membrane, which improves lactate export by MCT4; in accordance, metabolism characterized by reduced glycolysis and lactate production is effectively reprogrammed by SYVN1 knockdown, which can be reversed by MCT4 overexpression. Biologically, SYVN1 knockdown successfully compromises cell proliferation and tumour xenograft growth in mouse models that can be partially rescued by overexpression of MCT4. Clinicopathologically, overexpression of SYVN1 is associated with poor prognosis in patients with LUAD, highlighting the importance of the SYVN1-MCT4 axis, which performs metabolic reprogramming during the progression of LUAD.
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