ArticleMolecular cancer research : MCR2022
Hypoxia Drives Centrosome Amplification in Cancer Cells via HIF1α-dependent Induction of Polo-Like Kinase 4.
Article in Molecular cancer research : MCR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Oxidative stress and serum deprivation influence the evolution of newly formed tetraploid cells during tumorigenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Pervasive chromosomal instability drives the karyotypic evolution of hypodiploid tumours.Genome medicine · 2026Article
- Polo-like kinase 4 (PLK4) as a therapeutic target in breast cancer.Carcinogenesis · 2025Review
- Article
- Tumour hypoxia in driving genomic instability and tumour evolution.Nature reviews. Cancer · 2025Review
- Prolonged overexpression of PLK4 leads to formation of centriole rosette clusters that are connected via canonical centrosome linker proteins.Scientific reports · 2024Article
- Molecular landscape and functional characterization of centrosome amplification in ovarian cancer.Nature communications · 2023Article
- The fate of extra centrosomes in newly formed tetraploid cells: should I stay, or should I go?Frontiers in cell and developmental biology · 2023Review
- Aberrant expression of polo-like kinase 4 in renal cell carcinoma: Association with clinicopathological characteristics and long-term survival.Oncology letters · 2022Article
- Adaptation to Hypoxia May Promote Therapeutic Resistance to Androgen Receptor Inhibition in Triple-Negative Breast Cancer.International journal of molecular sciences · 2022Review
- Centrosome Defects in Hematological Malignancies: Molecular Mechanisms and Therapeutic Insights.Blood science (Baltimore, Md.) · 2022Review
- Balancing the scales: fine-tuning Polo-like kinase 4 to ensure proper centriole duplication.Genes & development · 2022Review
- PLK4 is upregulated in prostate cancer and its inhibition reduces centrosome amplification and causes senescence.The Prostate · 2022Article
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Authors and funding
18 authors at 6 institutions in 4 countries.
Funding
Abstract
Centrosome amplification (CA) has been implicated in the progression of various cancer types. Although studies have shown that overexpression of PLK4 promotes CA, the effect of tumor microenvironment on polo-like kinase 4 (PLK4) regulation is understudied. The aim of this study was to examine the role of hypoxia in promoting CA via PLK4. We found that hypoxia induced CA via hypoxia-inducible factor-1α (HIF1α). We quantified the prevalence of CA in tumor cell lines and tissue sections from breast cancer, pancreatic ductal adenocarcinoma (PDAC), colorectal cancer, and prostate cancer and found that CA was prevalent in cells with increased HIF1α levels under normoxic conditions. HIF1α levels were correlated with the extent of CA and PLK4 expression in clinical samples. We analyzed the correlation between PLK4 and HIF1A mRNA levels in The Cancer Genome Atlas (TCGA) datasets to evaluate the role of PLK4 and HIF1α in breast cancer and PDAC prognosis. High HIF1A and PLK4 levels in patients with breast cancer and PDAC were associated with poor overall survival. We confirmed PLK4 as a transcriptional target of HIF1α and demonstrated that in PLK4 knockdown cells, hypoxia-mimicking agents did not affect CA and expression of CA-associated proteins, underscoring the necessity of PLK4 in HIF1α-related CA. To further dissect the HIF1α-PLK4 interplay, we used HIF1α-deficient cells overexpressing PLK4 and showed a significant increase in CA compared with HIF1α-deficient cells harboring wild-type PLK4. These findings suggest that HIF1α induces CA by directly upregulating PLK4 and could help us risk-stratify patients and design new therapies for CA-rich cancers. IMPLICATIONS: Hypoxia drives CA in cancer cells by regulating expression of PLK4, uncovering a novel HIF1α/PLK4 axis.
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