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Regulative Loop between β-catenin and Protein Tyrosine Receptor Type γ in Chronic Myeloid Leukemia

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submitted on 2024-05-15, 11:39 and posted on 2024-05-15, 11:40 authored by Luisa Tomasello, Marzia Vezzalini, Christian Boni, Massimiliano Bonifacio, Luigi Scaffidi, Mohamed Yassin, Nader Al-Dewik, Paul Takam Kamga, Mauro Krampera, Claudio Sorio

Protein tyrosine phosphatase receptor type γ (PTPRG) is a tumor suppressor gene, down-regulated in Chronic Myeloid Leukemia (CML) cells by the hypermethylation of its promoter region. β-catenin (CTNNB1) is a critical regulator of Leukemic Stem Cells (LSC) maintenance and CML proliferation. This study aims to demonstrate the antagonistic regulation between β-catenin and PTPRG in CML cells. The specific inhibition of PTPRG increases the activation state of BCR-ABL1 and modulates the expression of the BCR-ABL1- downstream gene β-Catenin. PTPRG was found to be capable of dephosphorylating β-catenin, eventually causing its cytosolic destabilization and degradation in cells expressing PTPRG. Furthermore, we demonstrated that the increased expression of β-catenin in PTPRG-negative CML cell lines correlates with DNA (cytosine-5)-methyl transferase 1 (DNMT1) over-expression, which is responsible for PTPRG promoter hypermethylation, while its inhibition or down-regulation correlates with PTPRG re-expression. We finally confirmed the role of PTPRG in regulating BCR-ABL1 and β-catenin phosphorylation in primary human CML samples. We describe here, for the first time, the existence of a regulative loop occurring between PTPRG and β-catenin, whose reciprocal imbalance affects the proliferation kinetics of CML cells.

Other Information

Published in: International Journal of Molecular Sciences
License: https://creativecommons.org/licenses/by/4.0/
See article on publisher's website: https://dx.doi.org/10.3390/ijms21072298

Funding

Role of Protein Tyrosine Phosphatase Gamma (PTPRG) in the pathogenesis of chronic myeloid leukemia (CML) and its evaluation as a new biomarker of disease - https://app.dimensions.ai/details/grant/grant.4186376

History

Language

  • English

Publisher

MDPI

Publication Year

  • 2020

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • College of Health and Life Sciences - HBKU
  • Hamad Medical Corporation
  • Women's Wellness and Research Center - HMC
  • National Center for Cancer Care and Research - HMC
  • Academic Health System - HMC
  • Interim Translational Research Institute - HMC
  • Qatar University
  • Qatar University Health - QU
  • College of Medicine - QU HEALTH