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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

sFRP1 Expression Regulates Wnt Signaling in Chronic Myeloid Leukemia K562 Cells

Author(s): Melek Pehlivan*, Ceyda Caliskan, Zeynep Yuce and Hakki O. Sercan

Volume 22, Issue 7, 2022

Published on: 24 May, 2021

Page: [1354 - 1362] Pages: 9

DOI: 10.2174/1871520621666210524162145

Price: $65

Abstract

Background: Wnt signaling cascades play important roles in cell fate decisions and their deregulation has been documented in many diseases, including malignant tumors and leukemia. One mechanism of aberrant Wnt signaling is the silencing of Wnt inhibitors through epigenetic mechanisms. The sFRPs are one of the most studied Wnt inhibitors; and the sFRP1 loss is known in many hematological malignancies. Therefore, we aimed to compare the expression of Wnt related genes in the presence and absence of sFRP1 in a chronic myeloid leukemia (CML) cell line.

Objective: It is important to understand how sFRP1 and sFRP1 perform their effects on CML to design new agents and strategies for resistant and advanced forms of CML.

Materials and Methods: We used K562 cells, which normally do not express sFRP1 and its sFRP1 expressing subclone K562s. Total RNA was isolated from K562 and K562s cell lines and converted to cDNA. PCR Array experiments were performed using Human Wnt Signaling Pathway Plus RT2 Profiler™ kit. Wnt signaling pathway activation was studied by western blot for downstream signaling targets.

Results: The WNT3, LRP6, PRICKLE1 and BTRC expressions were significantly decreased in the presence of sFRP1; while WNT5B increased. The sFRP1 expression inhibited stabilization of total β-catenin protein and downstream effector phosphorylation of noncanonical Wnt/PCP signaling; whereas Ca2+/PKC signaling remained active.

Conclusion: The results suggest that sFRP1 could be a promising therapeutic anticancer agent. Defining these pathway interactions is crucial for designing new agents resistant and advanced forms of CML.

Keywords: Wnt signaling, chronic myeloid leukemia, sFRP1, epigenetics, gene expression, anticancer agents.

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