Dvl proteins regulate SMAD1, AHR, mTOR, BRD7 protein expression while differentially regulating canonical and non-canonical Wnt signaling pathways in CML cell lines

Çalışkan C., Yüce Z., Sercan H. O.

GENE, vol.20, no.854, pp.1-10, 2023 (SCI-Expanded)

  • Publication Type: Article / Article
  • Volume: 20 Issue: 854
  • Publication Date: 2023
  • Doi Number: 10.1016/j.gene.2022.147109
  • Journal Name: GENE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), Artic & Antarctic Regions, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.1-10
  • Dokuz Eylül University Affiliated: Yes

Abstract

Dishevelled (Dvl) is a scaffold protein that transmits Wnt signals to downstream effector

molecules via both canonical and non-canonical Wnt signaling pathways. Deregulated

activation of Dvl proteins has been reported in various solid tumors. However, it is not clear

which pathway and proteins are responsible for observed aberrant activities and their relevance

in disease prognosis. In addition, there is relatively limited knowledge on the role Dvl proteins

may have in hematologic malignancy etiopathogenesis. In this study, we demonstrated that Dvl

genes are not expressed in normal bone marrow but are expressed at different levels in the bone

marrow of patients with chronic myeloid leukemia. We showed SMAD1, AHR, mTOR, BRD7

protein expressions are significantly affected by Dvl silencing and overexpression in CML cell

lines. Wnt/-catenin and Wnt/PCP signaling pathway components are effectively repressed

after Dvl silencing in K562 cells, while regulator of Wnt/Ca2+ signaling showed increase in

both CML cell lines. Targeting Dvl proteins increases imatinib susceptibility of the K562 and

MEG-01 cell lines. In light of our data, Dvl could be a potential therapeutic target in the

treatment of CML.