Cited by 39Acute Myeloid Leukemia ResearchWnt/β-catenin signaling in development and cancerPI3K/AKT/mTOR signaling in cancer

GSK-3 as a novel prognostic indicator in leukemia

Ruvolo, Peter P.·2017·Advances in Biological Regulation

Abstract

While leukemias represent a diverse set of diseases with malignant cells derived from myeloid or lymphoid origin, a common feature is the dysregulation of signal transduction pathways that influence leukemogeneisis, promote drug resistance, and favor leukemia stem cells. Mutations in PI3K, PTEN, RAS, or other upstream regulators can activate the AKT kinase which has central roles in supporting cell proliferation and survival. A major target of AKT is Glycogen Synthase Kinase 3 (GSK3). GSK3 has two isoforms (alpha and beta) that were studied as regulators of metabolism but emerged as central players in cancer in the early 1990s. GSK3 is unique in that the isoforms are constitutively active. Active GSK3 promotes destruction of oncogenic proteins such as beta Catenin, c-MYC, and MCL-1 and thus has tumor suppressor properties. In AML, inactivation of GSK3 is associated with poor overall survival. Interestingly in some leukemias GSK3 targets a tumor suppressor and thus the kinases can act as tumor promoters in those instances. An example is GSK3 targeting p27Kip1 in AML with MLL translocation. This review will cover the role of GSK3 in various leukemias both as tumor suppressor and tumor promoter. We will also briefly cover current state of GSK3 inhibitors for leukemia therapy.

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Crossref · 10.1016/j.jbior.2017.05.001

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119 of 119 references verified0 citation errors · 0 not checkable

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  • GSK3β is constitutively active and acts as tumor suppressor in solid tumors by promoting proteolysis of oncogenic proteins such as β-catenin, c-myc, MCL1.

    “GSK3b is constitutively active and has been shown to act as tumor suppressor by promoting proteolysis of key oncogenic proteins such as b-catenin, c-myc, MCL1, etc. in solid tumors (11).”
  • GSK3 regulates multiple cellular processes including cell growth, differentiation, and apoptosis in response to environmental stimuli.

    “GSK3, originally identified as a key enzyme of glycolytic pathway, was subsequently shown to regulate multiple cellular processes, including cell growth, differentiation, and apoptosis in response to explicit environmental stimuli (11,33).”

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Authors
Ruvolo, P. P.
Affiliations
The University of Texas MD Anderson Cancer Center (US)
Corresponding author
Ruvolo, Peter P.
Venue
Advances in Biological Regulation
Publisher
Elsevier BV
Published
2017-08
Volume
65
Pages
26-35
ISSN
2212-4926 (ISSN-L)
OpenAlex
W2613848997
Cited by
39
References
123
Citations by year
2025: 4 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 7 · 2019: 4 · 2018: 10 · 2017: 6
FWCI
1.16
Type
journal article
Language
en
Open access
closed
Locations
  • Advances in Biological Regulation (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords
glycogen synthase kinase-3, leukemia, prognostic factors, acute myeloid leukemia, MLL translocation, p27, Akt signaling, tumor suppressor, tumor promoters, GSK-3 inhibitors, leukemia stem cells, drug resistance
MeSH terms
Antineoplastic Agents, Humans, Leukemia, Prognosis, Signal Transduction, Gene Expression Regulation, Leukemic, Survival Analysis, Proto-Oncogene Proteins c-myc, ras Proteins, Phosphatidylinositol 3-Kinases, Protein Isoforms, Glycogen Synthase Kinase 3, Proto-Oncogene Proteins c-akt, PTEN Phosphohydrolase, beta Catenin, Myeloid Cell Leukemia Sequence 1 Protein

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