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

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.

Activation of LXR β inhibits tumor respiration and is synthetically lethal with Bcl‐ xL inhibition

“…Dried polar extracts were reconstituted in 100 μl water, and lipid extracts were reconstituted in 50 μl, 65:30:5 acetonitrile:2‐propanol:water ( v / v / v ). Both polar and lipid samples were analyzed using LC‐HRMS by the Whitehead Institute Metabolite Profiling Core Facility (Cambridge, MA) as previously described (Franco et al , ; Gui et al , ; Keckesova et al , ). Polar metabolites were analyzed by metabolite set enrichment analysis ( http://www.metaboanalyst.ca).…”

Upregulation of miR‐374a promotes tumor metastasis and progression by downregulating LACTB and predicts unfavorable prognosis in breast cancer

“…Overexpression of LACTB could inhibit the proliferation, invasion, and angiogenesis of glioma cells by regulating expression of PCNA, MMP2, MMP9, and VEGF . All these results indicated LACTB was a bona fide new tumor suppressor . However, the relationship between LACTB expression and prognosis in BRCA, as well as the regulatory network of LACTB remain largely unclear.…”

El cáncer visto desde la mirilla metabólica

“…Curiosamente, y volviendo al descubrimiento de Warburg, la pérdida de PGC1A aumenta el metabolismo glicolítico, de modo que promueve la producción de biomasa y con ello el crecimiento del tumor una vez se disemina. En un reciente estudio de unas de las grandes mentes en la investigación del cáncer, Bob Weinberg, retoma una evidencia de décadas atrás para formular una hipótesis relevante (9). Este modo de desarrollar un proyecto (o de concebir la hipótesis) apoya la idea de que, a pesar de los recursos tecnológicos de que dispongamos, sin una buena pregunta que formular difícilmente podremos alcanzar conclusiones relevantes para avanzar en la investigación en cáncer (10).…”