LACTB is a tumour suppressor that modulates lipid metabolism and cell state

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

Research output: Contribution to journalArticlepeer-review

130 Scopus citations

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.

Original languageEnglish
Pages (from-to)681-686
Number of pages6
JournalNature
Volume543
Issue number7647
DOIs
StatePublished - 30 Mar 2017
Externally publishedYes

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