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Cited by 22Cancer-related Molecular PathwaysCancer, Hypoxia, and MetabolismUbiquitin and proteasome pathways

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APC/C-CDH1–Regulated IDH3β Coordinates with the Cell Cycle to Promote Cell Proliferation

Wu, Qingnan, Zhang, Weimin, Xue, Liyan, Wang, Yan, Fu, Ming, Ma, Liying, Song, Yongmei, Zhan, Qi-Min·2019·Cancer Research
DOI 10.1158/0008-5472.can-18-2341

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Abstract

Metabolic activities are often accompanied by cell-cycle progression, yet known connections between these two processes remain limited. Here, we identified the isocitrate dehydrogenase 3β (IDH3β) as a novel substrate of anaphase-promoting complex/cyclosome (APC/C)-CDH1 and an important regulator of the cell cycle. In esophageal squamous cell carcinoma (ESCC), IDH3β was posttranslationally upregulated in late G1 phase, and overexpression of IDH3β accelerated G1–S transition, contributing to the promotion of cell proliferation in vitro and in vivo. α-Ketoglutarate (α-KG), a crucial metabolite in tricarboxylic acid (TCA) cycle, was dependent on IDH3β level and partially accounted for IDH3β-mediated cell growth. IDH3β expression increased PFKFB3 protein levels and enhanced glucose uptake, and high expression of IDH3β correlated with poor survival in patients with ESCC, suggesting a potential application of IDH3β in prognosis. Overall, our results highlight a new molecular connection between cell-cycle regulation and the TCA cycle in ESCC. Significance: These findings show that IDH3β is an APC/C-CDH1 substrate and is expressed in a cell-cycle–dependent manner, highlighting novel molecular cross-talk between the TCA cycle and cell cycle in cancer cells.

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Metadata

Authors
Wu, Q., Zhang, W., Xue, L., Wang, Y., Fu, M., Ma, L., Song, Y., & Zhan, Q.-M.
Affiliations
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
  • Peking University Cancer Hospital (CN)
  • 1State Key Laboratory of Molecular Oncology, National Cancer center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
ORCID
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2019-07-01
Volume
79
Issue
13
Pages
3281-3293
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
DOI
10.1158/0008-5472.can-18-2341
OpenAlex
W2943519216
Cited by
22
References
6
Citations by year
2026: 2 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 1
FWCI
0.73
Type
journal article
Language
en
Open access
closed
Locations
  • Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81490753)
  • National Basic Research Program of China (2015CB553904)
  • China Postdoctoral Science Foundation (2017M620010)
  • National Key Research and Development Program of China (2016YFA0500303)
Topics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Keywords
anaphase-promoting complex, CDH1, cell cycle regulation, G1/S transition, esophageal squamous cell carcinoma, TCA cycle, alpha-ketoglutarate, PFKFB3, glucose uptake, cell proliferation, prognostic factors
MeSH terms
Esophageal Squamous Cell Carcinoma, Animals, Cell Cycle, Esophageal Neoplasms, Female, Humans, Isocitrate Dehydrogenase, Male, Mice, Inbred BALB C, Mice, Nude, Middle Aged, Neoplasm Metastasis, Prognosis, Tumor Cells, Cultured, Biomarkers, Tumor, Antigens, CD, Cadherins, Gene Expression Regulation, Neoplastic, Survival Rate, Apoptosis, Xenograft Model Antitumor Assays, Cell Proliferation, Mice, Anaphase-Promoting Complex-Cyclosome

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