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Cited by 885PI3K/AKT/mTOR signaling in cancerProtein Kinase Regulation and GTPase SignalingMetabolism, Diabetes, and Cancer

Multiple Roles of the PI3K/PKB (Akt) Pathway in Cell Cycle Progression

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Liang, Jiyong, Slingerland, Joyce M.·2003·Cell Cycle
DOI 10.4161/cc.2.4.433
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Abstract

As its role in tumor progression emerges, the PI3K/PKB (Akt) pathway presents an appealing cancer therapeutic target. Recent studies have investigated the mechanisms underlying the tumor-promoting effects of this pathway. PKB triggers a network that positively regulates G1/S cell cycle progression through inactivation of GSK3-beta, leading to increased cyclin D1, and inhibition of Forkhead family transcription factors and the tumor suppressor tuberin (TSC2), leading to reduction of p27Kip1. The identification of p21Waf1/Cip1 and p27Kip1 as novel substrates of PKB provided new insights into mechanisms whereby hyperactivation of this lipid signaling pathway may lead to cell cycle deregulation in human cancers. The PI3K pathway may also play a key role in the G2/M transition and its constitutive activation may lead to defects in DNA damage checkpoint control.

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  • GSK-3β has several downstream targets and is a regulator in many pathways, including Wnt, PI3K and Hedgehog signaling.

    “GSK-3β has several downstream targets and is a regulator in many pathways, including Wnt, PI3K and Hedgehog signaling (104–106).”

    From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [105]

    The section on PKB in G1/S progression describes GSK-3β acting on cyclin D1 and c-Myc and being inhibited by PKB, supporting multiple targets and a role in PI3K/PKB signaling. The passages do not address a role for GSK-3β in Wnt or Hedgehog signaling (searched: Wnt, Hedgehog). Page numbers were not provided. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Cited by

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Authors
Liang, J., & Slingerland, J. M.
Affiliations
  • Sunnybrook Health Science Centre (CA)
  • University of Miami (US)
ORCID
Slingerland, Joyce M.
Venue
Cell Cycle
Publisher
Informa UK Limited
Published
2003-07
Volume
2
Issue
4
Pages
336-342
ISSN
  • 1538-4101 (ISSN-L)
  • 1551-4005
DOI
10.4161/cc.2.4.433
OpenAlex
W2035258932
Cited by
885
References
0
Citations by year
2026: 8 · 2025: 17 · 2024: 16 · 2023: 38 · 2022: 33 · 2021: 26 · 2020: 27 · 2019: 35 · 2018: 40 · 2017: 33 · 2016: 37 · 2015: 61 · 2014: 52 · 2013: 59 · 2012: 61
FWCI
9.44
Type
journal article
Language
en
Open access
Locations
  • Cell Cycle (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
PI3K/Akt signaling, cell cycle progression, G1/S transition, cyclin D1, forkhead transcription factor, p27, p21, G2/M transition, DNA damage checkpoint, tumor progression, cancer therapy targets
MeSH terms
Glycogen Synthase Kinase 3 beta, Tuberous Sclerosis Complex 2 Protein, Animals, Blood Proteins, Cell Cycle, Enzyme Activation, Phosphorylation, Proteins, Proto-Oncogene Proteins, Repressor Proteins, Signal Transduction, Cyclins, Proto-Oncogene Proteins c-myc, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Phosphatidylinositol 3-Kinases, Cyclin D1, Tumor Suppressor Proteins, Protein Interaction Mapping, Glycogen Synthase Kinase 3, Retinoblastoma-Like Protein p130, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinase Inhibitor p27, Proto-Oncogene Proteins c-akt, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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