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Propionate reinforces epithelial identity and reduces aggressiveness of non-small cell lung carcinoma via chromatin remodelling

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE224741 | GEO | 2023/02/15

REPOSITORIES: GEO

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Propionate reinforces epithelial identity and reduces aggressiveness of lung carcinoma

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Propionate reinforces epithelial identity and reduces aggressiveness of non-small cell lung carcinoma via chromatin remodelling [ChIP-seq]

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Project description:The alteration of metabolic pathways is a critical strategy for cancer cells to attain the traits necessary for metastasis in disease progression. We found that dysregulation of propionate metabolism occurs through TGFbeta- and ERK2-driven downregulation of methylmalonyl-CoA epimerase (MCEE). MCEE downregulation occurs through a transcription factor Sp1/EGR1 switch at its promoter region, resulting in reduced flux through this anapleurotic pathway and leading to accumulation of methylmalonic acid (MMA), a byproduct of the propionate metabolism. MMA accumulation through alteration of propionate metabolism produces a pro-aggressive signature in breast and lung cancer cells and increases their metastatic potential. Altogether, we present a previously uncharacterized dysregulation of propionate metabolism as a novel contributor to cancer and a valuable potential target in the therapeutic treatment of metastatic carcinomas.

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