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Role of Protein Tyrosine Phosphatase Receptor Type E (PTPRE) in Chemoresistant Retinoblastoma

Lars Mohren1, Annika Doege1, Natalia Miroschnikov2

  • 1Institute for Anatomy II, Department of Neuroanatomy, Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Medical Faculty, University of Duisburg-Essen, 45122 Essen, Germany.

International Journal of Molecular Sciences
|April 27, 2024
PubMed

Insights

Protein tyrosine phosphatase receptor type E (PTPRE) drives chemoresistant retinoblastoma (RB) growth. Lowering PTPRE levels in RB cells reduced tumor growth, increased apoptosis, and restored etoposide sensitivity, indicating PTPRE

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Protein tyrosine phosphatase receptor type E (PTPRE) is implicated in various cancers.
  • The role of PTPRE in retinoblastoma (RB), particularly chemoresistant forms, is not well understood.

Purpose of the Study:

  • To investigate the role of PTPRE in the development and progression of chemoresistant retinoblastoma.
  • To explore potential therapeutic strategies targeting PTPRE in RB.

Main Methods:

  • Analysis of PTPRE expression in RB cell lines and patient samples.
  • Lentiviral PTPRE knockdown (KD) in RB cells.
  • In vivo studies using the chicken chorioallantoic membrane (CAM) assay.
  • Investigation of microRNA (miRNA) regulation and downstream signaling pathways.

Main Results:

  • PTPRE expression is significantly elevated in etoposide-resistant RB cells and patients.
  • PTPRE KD reduced RB cell proliferation, viability, and tumor formation in vivo, while increasing apoptosis and etoposide sensitivity.
  • miR631 was downregulated in chemoresistant RB and its overexpression mimicked PTPRE KD effects.
  • PTPRE KD altered phosphorylation of SGK3, AKT, and ERK1/2 signaling pathways.

Conclusions:

  • PTPRE plays an oncogenic role in chemoresistant retinoblastoma.
  • PTPRE represents a potential therapeutic target for overcoming etoposide resistance in RB.
  • miR631 may regulate PTPRE in RB, and PTPRE influences key signaling pathways involved in cell survival and proliferation.
Keywords:
CAM assayPTPREchemoresistanceetoposidemiR631retinoblastomatumorigenesis

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