Nutrient control of splice site selection contributes to methionine addiction of cancer.

ABSTRACT:

Objective

Many cancer cells depend on exogenous methionine for proliferation, whereas non-tumorigenic cells can divide in media supplemented with the metabolic precursor homocysteine. This phenomenon is known as methionine dependence of cancer or methionine addiction. The underlying mechanisms driving this cancer-specific metabolic addiction are poorly understood. Here we find that methionine dependence is associated with severe dysregulation of pre-mRNA splicing.

Methods

We used triple-negative breast cancer cells and their methionine-independent derivatives R8 to compare RNA expression profiles in methionine and homocysteine growth media. The data set was also analyzed for alternative splicing.

Results

When tumorigenic cells were cultured in homocysteine medium, can

SUBMITTER: Lin DW 

PROVIDER: S-EPMC11834112 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature