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Article Dans Une Revue Cancers Année : 2020

Merkel cell polyomavirus T antigens induce Merkel cell-like differentiation in GLI1-expressing epithelial cells

Patricia Berthon
Aurélie Sallot
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Théo Gandon
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Christophe Destrieux
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Antoine Touzé

Résumé

Merkel cell carcinoma (MCC) is an aggressive skin cancer frequently caused by the Merkel cell polyomavirus (MCPyV). It is still under discussion, in which cells viral integration and MCC development occurs. Recently, we demonstrated that a virus-positive MCC derived from a trichoblastoma, an epithelial neoplasia bearing Merkel cell (MC) differentiation potential. Accordingly, we hypothesized that MC progenitors may represent an origin of MCPyV-positive MCC. To sustain this hypothesis, phenotypic comparison of trichoblastomas and physiologic human MC progenitors was conducted revealing GLI family zinc finger 1 (GLI1), Keratin 17 (KRT 17), and SRY-box transcription factor 9 (SOX9) expressions in both subsets. Furthermore, GLI1 expression in keratinocytes induced transcription of the MC marker SOX2 supporting a role of GLI1 in human MC differentiation. To assess a possible contribution of the MCPyV T antigens (TA) to the development of an MC-like phenotype, human keratinocytes were transduced with TA. While this led only to induction of KRT8, an early MC marker, combined GLI1 and TA expression gave rise to a more advanced MC phenotype with SOX2, KRT8, and KRT20 expression. Finally, we demonstrated MCPyV-large T antigens' capacity to inhibit the degradation of the MC master regulator Atonal bHLH transcription factor 1 (ATOH1). In conclusion, our report suggests that MCPyV TA contribute to the acquisition of an MC-like phenotype in epithelial cells.
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hal-02951400 , version 1 (28-09-2020)

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Thibault Kervarrec, Mahtab Samimi, Sonja Hesbacher, Patricia Berthon, Marion Wobser, et al.. Merkel cell polyomavirus T antigens induce Merkel cell-like differentiation in GLI1-expressing epithelial cells. Cancers, 2020, 12 (7), 20 p. ⟨10.3390/cancers12071989⟩. ⟨hal-02951400⟩
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