Abstract
<div>AbstractPurpose:<p>Thyroid cancer metabolic characteristics vary depending on the molecular subtype determined by mutational status. We aimed to investigate the molecular subtype-specific metabolic characteristics of thyroid cancers.</p>Experimental Design:<p>An integrative multi-omics analysis was conducted, incorporating transcriptomics, metabolomics, and proteomics data obtained from human tissues representing distinct molecular characteristics of thyroid cancers: <i>BRAF</i>-like (papillary thyroid cancer with <i>BRAF</i><sup>V600E</sup> mutation; PTC-B), <i>RAS</i>-like (follicular thyroid cancer with <i>RAS</i> mutation; FTC-R), and ATC-like (anaplastic thyroid cancer with <i>BRAF</i><sup>V600E</sup> or <i>RAS</i> mutation; ATC-B or ATC-R). To validate our findings, we employed tissue microarray of human thyroid cancer tissues and performed <i>in vitro</i> analyses of cancer cell phenotypes and metabolomic assays after inducing genetic knockdown.</p>Results:<p>Metabolic properties differed between differentiated thyroid cancers of PTC-B and FTC-R, but were similar in dedifferentiated thyroid cancers of ATC-B/R, regardless of their mutational status. Tricarboxylic acid (TCA) intermediates and branched-chain amino acids (BCAA) were enriched with the activation of TCA cycle only in FTC-R, whereas one-carbon metabolism and pyrimidine metabolism increased in both PTC-B and FTC-R and to a great extent in ATC-B/R. However, the protein expression levels of the BCAA transporter (SLC7A5) and a key enzyme in one-carbon metabolism (SHMT2) increased in all thyroid cancers and were particularly high in ATC-B/R. Knockdown of <i>SLC7A5</i> or <i>SHMT2</i> inhibited the migration and proliferation of thyroid cancer cell lines differently, depending on the mutational status.</p>Conclusions:<p>These findings define the metabolic properties of each molecular subtype of thyroid cancers and identify metabolic vulnerabilities, providing a rationale for therapies targeting its altered metabolic pathways in advanced thyroid cancer.</p></div>
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call