{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T02:31:17Z","timestamp":1789525877708,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2014,4,30]],"date-time":"2014-04-30T00:00:00Z","timestamp":1398816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Molecular tumour targeting has significantly improved anti\u2010cancer protocols. Still, the addition of molecular targeting to the treatment regime has not led to a curative breakthrough. Combined mammalian target of <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>apamycin (m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content>) and histone deacetylase (<jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>) inhibition has been shown not only to enhance anti\u2010tumour potential, but also to prevent resistance development seen under mono\u2010drug therapy. This investigation was designed to evaluate whether cross\u2010communication exists between m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content> signalling and epigenetic events regulated by <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">DU<\/jats:styled-content>\u2010145 prostate cancer cells were treated with insulin\u2010like growth factor (<jats:styled-content style=\"fixed-case\">IGF<\/jats:styled-content>) to activate the Akt\u2010m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content> cascade or with the <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>\u2010inhibitor valproic acid (<jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>) to induce histone H3 and H4 acetylation (aH3, aH4). Subsequently, m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content>, Rictor, Raptor, p70s6k, Akt (all: total and phosphorylated), H3 and H4 (total and acetylated) were analysed by western blotting. Both techniques revealed a link between m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content> and the epigenetic machinery. <jats:styled-content style=\"fixed-case\">IGF<\/jats:styled-content> activated m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content>, Rictor, Raptor, p70s6k and Akt, but also enhanced aH3 and aH4. Inversely, <jats:styled-content style=\"fixed-case\">IGF<\/jats:styled-content>r blockade and knock\u2010down blocked the Akt\u2010m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content> axis, but simultaneously diminished aH3 and aH4. <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content> treatment up\u2010regulated histone acetylation, but also activated m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content>\u2010Akt signalling. <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>1 and 2 knock\u2010down revealed that the interaction with the m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content> system is initiated by histone H3 acetylation. <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>\u2010m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content> communication, therefore, is apparent whereby tumour\u2010promoting (Akt\/m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content><jats:sup>high<\/jats:sup>, aH3\/aH4<jats:sup>low<\/jats:sup>) and tumour\u2010suppressing signals (Akt\/m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content><jats:sup>low<\/jats:sup>, aH3\/aH4<jats:sup>high<\/jats:sup>) are activated in parallel. Combined use of an <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>\u2010 and m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content> inhibitor might then diminish pro\u2010tumour effects triggered by the <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>\u2010 (Akt\/m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content><jats:sup>high<\/jats:sup>) or m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content> inhibitor (aH3\/aH4<jats:sup>low<\/jats:sup>) alone.<\/jats:p>","DOI":"10.1111\/jcmm.12299","type":"journal-article","created":{"date-parts":[[2014,4,30]],"date-time":"2014-04-30T08:22:42Z","timestamp":1398846162000},"page":"1460-1466","source":"Crossref","is-referenced-by-count":28,"title":["Cross\u2010communication between histone H3 and H4 acetylation and Akt\u2010m<scp>TOR<\/scp> signalling in prostate cancer 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