Intracellular CYTL1, a novel tumor suppressor, stabilizes NDUFV1 to inhibit metabolic reprogramming in breast cancer.

ABSTRACT: Loss-of-function mutations frequently occur in tumor suppressor genes, i.e., p53, during the malignant progression of various cancers. Whether any intrinsic suppressor carries a rare mutation is largely unknown. Here, we demonstrate that intracellular cytokine-like protein 1 (CYTL1) plays a key role in preventing the robust glycolytic switching characteristic of breast cancer. A low intracellular CYTL1 level, not its mutation, is required for metabolic reprogramming. Breast cancer cells expressing an intracellular form of CYTL1 lacking a 1-22 aa signal peptide, ΔCYTL1, show significantly attenuated glucose uptake and lactate production, which is linked to the inhibition of cell growth and metastasis in vitro and in vivo. Mechanistically, CYTL1 competitively binds the N-terminal sequence of

SUBMITTER: Xue W 

PROVIDER: S-EPMC8813937 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature