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Updated: Aug 17, 2025

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
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Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

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Dvl proteins regulate SMAD1, AHR, mTOR, BRD7 protein expression while differentially regulating canonical and

Ceyda Caliskan1, Zeynep Yuce2, Hakki Ogun Sercan2

  • 1Department of Medical Biology and Genetics, Faculty of Medicine, Dokuz Eylul University, Balcova, Izmir, Turkey; School of Biosciences, University of Sheffield, Sheffield S10 2TN, United Kingdom.

Gene
|December 12, 2022
PubMed

Insights

Dishevelled (Dvl) proteins are expressed in chronic myeloid leukemia (CML) but not normal bone marrow. Targeting Dvl enhances imatinib effectiveness, suggesting Dvl as a potential CML therapeutic target.

Area of Science:

  • Molecular oncology
  • Hematologic malignancies
  • Signal transduction

Background:

  • Dishevelled (Dvl) proteins are crucial scaffold proteins in Wnt signaling pathways.
  • Dvl deregulation is implicated in solid tumors, but its role in hematologic malignancies is understudied.
  • Understanding Dvl's role in leukemia pathogenesis is critical for developing novel therapies.

Purpose of the Study:

  • To investigate the expression and role of Dvl proteins in chronic myeloid leukemia (CML).
  • To identify downstream signaling pathways affected by Dvl modulation in CML.
  • To evaluate the therapeutic potential of targeting Dvl in CML.

Main Methods:

  • Quantitative analysis of Dvl gene expression in normal and CML bone marrow.
  • Dvl silencing and overexpression experiments in CML cell lines (K562, MEG-01).
  • Assessment of downstream signaling pathway components (SMAD1, AHR, mTOR, BRD7, Wnt/β-catenin, Wnt/PCP, Wnt/Ca2+).
  • Evaluation of imatinib susceptibility following Dvl targeting.

Main Results:

  • Dvl genes are expressed in CML bone marrow but absent in normal bone marrow.
  • Dvl modulation significantly impacts SMAD1, AHR, mTOR, and BRD7 protein levels in CML cells.
  • Dvl silencing represses Wnt/β-catenin and Wnt/PCP pathways while activating Wnt/Ca2+ signaling.
  • Targeting Dvl enhances the sensitivity of CML cells to imatinib.

Conclusions:

  • Dvl proteins play a significant role in the pathogenesis of CML.
  • Dvl is a potential therapeutic target for CML treatment.
  • Combined targeting of Dvl and imatinib may offer a novel therapeutic strategy for CML.
Keywords:
Dvl1siRNA silencing−2,-3, Chronic myeloid leukemia

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