LACTB is a Tumour Suppressor That Modulates Lipid Metabolism and Cell State

Overview

Journal Nature

Specialty Science

Date 2017 Mar 23

PMID 28329758

Citations 85

Authors

Zuzana Keckesova

Joana Liu Donaher

Jasmine De Cock

Elizaveta Freinkman

Susanne Lingrell

Daniel A Bachovchin

Brian Bierie

Verena Tischler

Aurelia Noske

Marian C Okondo

Ferenc Reinhardt

Prathapan Thiru

Todd R Golub

Jean E Vance

Robert A Weinberg

Affiliations

Soon will be listed here.

Abstract

Post-mitotic, differentiated cells exhibit a variety of characteristics that contrast with those of actively growing neoplastic cells, such as the expression of cell-cycle inhibitors and differentiation factors. We hypothesized that the gene expression profiles of these differentiated cells could reveal the identities of genes that may function as tumour suppressors. Here we show, using in vitro and in vivo studies in mice and humans, that the mitochondrial protein LACTB potently inhibits the proliferation of breast cancer cells. Its mechanism of action involves alteration of mitochondrial lipid metabolism and differentiation of breast cancer cells. This is achieved, at least in part, through reduction of the levels of mitochondrial phosphatidylserine decarboxylase, which is involved in the synthesis of mitochondrial phosphatidylethanolamine. These observations uncover a novel mitochondrial tumour suppressor and demonstrate a connection between mitochondrial lipid metabolism and the differentiation program of breast cancer cells, thereby revealing a previously undescribed mechanism of tumour suppression.

Citing Articles

The Pivotal Role of LACTB in the Process of Cancer Development.

Zhang M, Wu B, Gu J Int J Mol Sci. 2025; 26(3).

PMID: 39941048 PMC: 11818536. DOI: 10.3390/ijms26031279.

EBV-miR-BART14-3p Targets LACTB to Enhance Gastric Cancer Cell Proliferation and Migration.

Huang X, Zhao X, Qi Y, Lan T, Wang R, Liang S Biochem Genet. 2025; .

PMID: 39903432 DOI: 10.1007/s10528-025-11033-2.

Unlocking the Hidden Potential of Cancer Therapy Targeting Lysine Succinylation.

Zheng Z, Xiao P, Kuang J, Wang Z, Wang X, Huang D J Cancer. 2025; 16(3):821-834.

PMID: 39781339 PMC: 11705062. DOI: 10.7150/jca.105849.

Lysophosphatidylethanolamine improves diastolic dysfunction by alleviating mitochondrial injury in the aging heart.

Xu G, Xiao W, Sun P, Sun Y, Yang X, Yin X J Lipid Res. 2024; 66(1):100713.

PMID: 39579983 PMC: 11719853. DOI: 10.1016/j.jlr.2024.100713.

Diagnosis and prognosis prediction of gastric cancer by high-performance serum lipidome fingerprints.

Cai Z, Wang W, Chen D, Chen H, Hu Y, Luo X EMBO Mol Med. 2024; 16(12):3089-3112.

PMID: 39543322 PMC: 11628598. DOI: 10.1038/s44321-024-00169-0.

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