Work

ECHS1 modulates hypoxia-associated PGK1 crotonylation and malignant phenotypes in prostate cancer models

Year: 2026

Type: article

Abstract: Hypoxia promotes metabolic adaptation and aggressive behavior in prostate cancer, but the contribution of lysine crotonylation to this response is incompletely defined. This study examined whether enoyl-CoA hydratase 1 (ECHS1) is associated with hypoxia-responsive phosphoglycerate kinase 1 (PGK1) crotonylation and malignant phenotypes. ECHS1 expression and prognosis were evaluated using The Cancer Genome Atlas. PC-3 and LNCaP cells were exposed to 1% O₂ for up to 24 h. Protein crotonylation, ECHS1, and PGK1 were assessed by immunoblotting and immunoprecipitation; gene expression, lactate, stemness-associated markers, migration, and invasion were also examined. PGK1 K131R and ECHS1 knockdown were used for functional analyses, and ECHS1-depleted PC-3 xenografts were evaluated in vivo. ECHS1 mRNA was higher in prostate tumors than in normal tissue, and high expression was associated with shorter disease-free survival. Hypoxia increased a prominent 83-kDa pan-Kcr-reactive signal in whole-cell lysates and ECHS1 expression but reduced PGK1-associated crotonylation without materially changing total PGK1. The K131R construct showed lower PGK1 crotonylation and was accompanied by lower lactate, HK2, LDHA, MCT4, CD44, CD133, and Oct4 readouts and fewer migrating and invading cells than the hypoxia group. ECHS1 knockdown increased PGK1-associated crotonylation and lowered HIF1A mRNA relative to hypoxia. Xenografts established from ECHS1-depleted cells had smaller endpoint tumor volumes than control xenografts. ECHS1 was associated with hypoxia-responsive PGK1 crotonylation and glycolytic and invasive phenotypes in prostate cancer models. Genetic ECHS1 depletion increased PGK1-associated crotonylation and reduced xenograft growth, supporting a functional contribution of ECHS1 within the tested systems. Not applicable.

Source: BMC Molecular and Cell Biology

DOI: 10.1186/s12860-026-00605-8

Authors: Xiangfu Meng, Song Zhang, Maoli Sun, Wencai Zhang, Chuang Li

Institution: Qiqihar Medical University

Language: English

Topic: Cancer, Hypoxia, and Metabolism

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,390