TY - JOUR
T1 - WNT Signaling in Hematological Malignancies
AU - Frenquelli, Michela
AU - Tonon, Giovanni
N1 - Funding Information:
Funding for this research was provided by Fondazione Cariplo, Association for International Cancer Research (AICR no. 09-0713 to GT), Associazione Italiana per la Ricerca sul Cancro (AIRC Special Program Molecular Clinical Oncology, 5 per mille no. 9965 to GT), Multiple Myeloma Research Foundation (MMRF Research Fellow Award to MF), and Ministero della salute (GR-2011-02351686 to MF).
Publisher Copyright:
© Copyright © 2020 Frenquelli and Tonon.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2020/12/21
Y1 - 2020/12/21
N2 - The role of the WNT signaling pathway in key cellular processes, such as cell proliferation, differentiation and migration is well documented. WNT signaling cascade is initiated by the interaction of WNT ligands with receptors belonging to the Frizzled family, and/or the ROR1/ROR2 and RYK families. The downstream signaling cascade results in the activation of the canonical β-catenin dependent pathway, ultimately leading to transcriptional control of cell proliferation, or the non-canonical pathway, mainly acting on cell migration and cell polarity. The high level of expression of both WNT ligands and WNT receptors in cancer cells and in the surrounding microenvironment suggests that WNT may represent a central conduit of interactions between tumor cells and microenviroment. In this review we will focus on WNT pathways deregulation in hematological cancers, both at the ligand and receptor levels. We will review available literature regarding both the classical β-catenin dependent pathway as well as the non-canonical pathway, with particular emphasis on the possible exploitation of WNT aberrant activation as a therapeutic target, a notion supported by preclinical data.
AB - The role of the WNT signaling pathway in key cellular processes, such as cell proliferation, differentiation and migration is well documented. WNT signaling cascade is initiated by the interaction of WNT ligands with receptors belonging to the Frizzled family, and/or the ROR1/ROR2 and RYK families. The downstream signaling cascade results in the activation of the canonical β-catenin dependent pathway, ultimately leading to transcriptional control of cell proliferation, or the non-canonical pathway, mainly acting on cell migration and cell polarity. The high level of expression of both WNT ligands and WNT receptors in cancer cells and in the surrounding microenvironment suggests that WNT may represent a central conduit of interactions between tumor cells and microenviroment. In this review we will focus on WNT pathways deregulation in hematological cancers, both at the ligand and receptor levels. We will review available literature regarding both the classical β-catenin dependent pathway as well as the non-canonical pathway, with particular emphasis on the possible exploitation of WNT aberrant activation as a therapeutic target, a notion supported by preclinical data.
KW - microenvironment
KW - multiple myeloma
KW - ROR2
KW - WNT
KW - Wnt/b-catenin
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U2 - 10.3389/fonc.2020.615190
DO - 10.3389/fonc.2020.615190
M3 - Review article
AN - SCOPUS:85098784969
VL - 10
JO - Frontiers in Oncology
JF - Frontiers in Oncology
SN - 2234-943X
M1 - 615190
ER -