Ectopic activation of WNT signaling in human embryonal carcinoma cells and its effects in short- and long-term in vitro culture

Yaser Atlasi, Rebecca T van Dorsten, Andrea Sacchetti, Rosalie Joosten, J Wolter Oosterhuis, Leendert H J Looijenga, Riccardo Fodde

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Human embryonal carcinoma (EC) cells comprise the pluripotent stem cells of malignant non-seminomatous germ cell tumors (GCTs) and represent the malignant counterpart of embryonic stem cells (ESCs). WNT/β-catenin signaling has been implicated in regulating adult and embryonic stem cells although its role in EC cells is less investigated. Here, we studied WNT signaling in a panel of representative pluripotent and nullipotent human EC cell lines. We found that EC cell lines show distinct levels of intrinsic WNT signaling and respond differently to ectopic WNT activation. Short-term activation of WNT signaling induced a differentiation-response in the pluripotent EC cells (NT2 and NCCIT) whereas the nullipotent EC cells (TERA1 and 2102Ep) were refractory and maintained high levels of OCT4 and SSEA4 expression. Long-term activation of WNT signaling in NCCIT and, to a lesser extent, TERA1 cells led to (re)gain of OCT4 expression and a switch from SSEA4 to SSEA1 surface antigens ultimately resulting in OCT4+/SSEA4-/SSEA1+ profile. Cisplatin treatment indicated that the OCT4+/SSEA4-/SSEA1+ NCCIT cells became more resistant to chemotherapy treatment. Our findings are of particular interest for the GCT and ES cell biology and shed light on the role of WNT signaling in human EC cells.

Original languageEnglish
Article number11928
Pages (from-to)11928
JournalScientific Reports
Issue number1
Publication statusPublished - 15 Aug 2019


  • Cell Culture Techniques
  • Cell Differentiation/drug effects
  • Cell Line, Tumor
  • Cisplatin/pharmacology
  • Drug Resistance, Neoplasm/drug effects
  • Embryonal Carcinoma Stem Cells/metabolism
  • Humans
  • Stage-Specific Embryonic Antigens/metabolism
  • Time Factors
  • Wnt Signaling Pathway/drug effects


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