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<jats:title>Abstract</jats:title><jats:p>Anaplastic thyroid cancer (ATC) is a rare, aggressive form of undifferentiated thyroid cancer, which exhibits rapid progression and is almost universally fatal. At least a subset of ATC is thought to arise from pre-existing well-differentiated thyroid cancer, most frequently papillary thyroid cancer (PTC). While <jats:italic>PIK3CA</jats:italic> mutations are rare in PTC, they are common in ATC and tend to co-occur with <jats:italic>BRAF</jats:italic> mutations. This provided the rationale for our study to identify the potential role of <jats:italic>PIK3CA</jats:italic> mutations in the progression from well-differentiated to undifferentiated thyroid cancer. We introduced <jats:italic>PIK3CA</jats:italic><jats:sup>E545K</jats:sup> into the LAM1 PTC cell line, which carries a <jats:italic>BRAF</jats:italic><jats:sup>V600E</jats:sup> mutation. In culture, the engineered cell line (LAM1:<jats:italic>PIK3CA</jats:italic><jats:sup>E545K</jats:sup>) proliferated faster and demonstrated increased clonogenic potential relative to the parental line carrying an empty vector (LAM1<jats:sup>EV</jats:sup>). Both the LAM1<jats:sup>EV</jats:sup> and LAM1:<jats:italic>PIK3CA</jats:italic><jats:sup>E545K</jats:sup> edited lines were implanted into hind flanks of athymic nude mice for in vivo determination of disease progression. While tumour weights and volumes were not significantly higher in LAM1:<jats:italic>PIK3CA</jats:italic><jats:sup>E545K</jats:sup> mice, there was a decrease in expression of thyroid differentiation markers TTF-1, thyroglobulin, PAX8 and B-catenin, suggesting that introduction of <jats:italic>PIK3CA</jats:italic><jats:sup>E545K</jats:sup> led to dedifferentiation in vivo. Collectively, this study provides evidence of a role for <jats:italic>PIK3CA</jats:italic><jats:sup>E545K</jats:sup> in driving disease progression from a well-differentiated to an undifferentiated thyroid cancer; however, over-expression was not a determinant of an accelerated growth phenotype in ATC.</jats:p>
<jats:p><jats:bold>Graphical Abstract</jats:bold></jats:p>
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Hinweis
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DeepGreen-ID: ff8d6aca23874558b1bb406ec30745d5 ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
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