Transcription factor NKX2-1 drives serine and glycine synthesis addiction in cancer.

ABSTRACT:

Background

One-third of cancers activate endogenous synthesis of serine/glycine, and can become addicted to this pathway to sustain proliferation and survival. Mechanisms driving this metabolic rewiring remain largely unknown.

Methods

NKX2-1 overexpressing and NKX2-1 knockdown/knockout T-cell leukaemia and lung cancer cell line models were established to study metabolic rewiring using ChIP-qPCR, immunoblotting, mass spectrometry, and proliferation and invasion assays. Findings and therapeutic relevance were validated in mouse models and confirmed in patient datasets.

Results

Exploring T-cell leukaemia, lung cancer and neuroendocrine prostate cancer patient datasets highlighted the transcription factor NKX2-1 as putative driver of serine/glycine metabolism. We demonstr

SUBMITTER: Heylen E 

PROVIDER: S-EPMC10147615 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature