ArticleCommunications biology2021
Plk1, upregulated by HIF-2, mediates metastasis and drug resistance of clear cell renal cell carcinoma.
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 41 citations in OpenAlex.
- Antibody-Drug Conjugates in Lung Cancer: Promise, Progress, and Persistent Challenges.Current issues in molecular biology · 2026Review
- Targeting Prolyl 3-hydroxylase 1 inhibits pancreatic cancer progression and macrophage immunity.Nature communications · 2026Article
- Mechanisms of resistance to antibody-drug conjugates in cancer: molecular barriers and pharmacological solutions.Cancer chemotherapy and pharmacology · 2025Review
- The advantages and challenges of sorafenib combination therapy: Drug resistance, toxicity and future directions (Review).Oncology letters · 2025Review
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- Review
- Loss of SETD2 in wild-type VHL clear cell renal cell carcinoma sensitizes cells to STF-62247 and leads to DNA damage, cell cycle arrest, and cell death characteristic of pyroptosis.Molecular oncology · 2025Article
- Article
- Resistance to antibody-drug conjugates: A review.Acta pharmaceutica Sinica. B · 2025Review
- The Effect of HIF-2International journal of inflammation · 2025Review
- Molecular mechanisms of renal cell carcinoma metastasis and potential targets for therapy.Frontiers in cell and developmental biology · 2025Review
- Article
- Metformin synergizes with gilteritinib in treating FLT3-mutated leukemia via targeting PLK1 signaling.Cell reports. Medicine · 2024Article
- MED15 is upregulated by HIF-2α and promotes proliferation and metastasis in clear cell renal cell carcinoma via activation of SREBP-dependent fatty acid synthesis.Cell death discovery · 2024Article
- Article
- Combination of Anti-Angiogenics and Immunotherapies in Renal Cell Carcinoma Show Their Limits: Targeting Fibrosis to Break through the Glass Ceiling?Biomedicines · 2024Review
- Important functions and molecular mechanisms of aquaporins family on respiratory diseases: potential translational values.Journal of Cancer · 2024Review
- Inhibition of Polo-like kinase 1 (PLK1) triggers cell apoptosis via ROS-caused mitochondrial dysfunction in colorectal carcinoma.Journal of cancer research and clinical oncology · 2023Article
- A group of novel VEGF splice variants as alternative therapeutic targets in renal cell carcinoma.Molecular oncology · 2023Article
- The E3 ligase RBCK1 reduces the sensitivity of ccRCC to sunitinib through the ANKRD35-MITD1-ANXA1 axis.Oncogene · 2023Article
Corrections and comments
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Authors and funding
27 authors at 11 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polo-like kinase 1 (Plk1) expression is inversely correlated with survival advantages in many cancers. However, molecular mechanisms that underlie Plk1 expression are poorly understood. Here, we uncover a hypoxia-regulated mechanism of Plk1-mediated cancer metastasis and drug resistance. We demonstrated that a HIF-2-dependent regulatory pathway drives Plk1 expression in clear cell renal cell carcinoma (ccRCC). Mechanistically, HIF-2 transcriptionally targets the hypoxia response element of the Plk1 promoter. In ccRCC patients, high expression of Plk1 was correlated to poor disease-free survival and overall survival. Loss-of-function of Plk1 in vivo markedly attenuated ccRCC growth and metastasis. High Plk1 expression conferred a resistant phenotype of ccRCC to targeted therapeutics such as sunitinib, in vitro, in vivo, and in metastatic ccRCC patients. Importantly, high Plk1 expression was defined in a subpopulation of ccRCC patients that are refractory to current therapies. Hence, we propose a therapeutic paradigm for improving outcomes of ccRCC patients.
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Registered trials
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