ArticleCell death & disease2023
Hypoxia-induced PLOD2 promotes clear cell renal cell carcinoma progression via modulating EGFR-dependent AKT pathway activation.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Integrating proteomics and metabolomics to reveal MAT2A for metabolic reprogramming in non-small cell lung cancer cells.iScience · 2026Article
- Targeting PLOD2 induces epithelioid differentiation and improves therapeutic response in sarcomatoid renal cell carcinoma.Journal of advanced research · 2026Article
- Unveiling the epigenetic landscape: transforming renal cell carcinoma treatment.Clinical epigenetics · 2026Review
- Extracellular Matrix-Related Prognostic Signature for Head and Neck Squamous Cell Carcinoma via Multi-Algorithm Survival Modeling.Biomarker insights · 2026Article
- Hypoxia-Driven Immune Escape in Clear Cell Renal Cell Carcinoma: A Prognostic Model and Dual-Functional Biomarker PLOD2 for Immunotherapy Stratification.Journal of Cancer · 2026Article
- New Method Enhanced Extraction of Protein Signatures of Renal Cell Carcinoma from Proteomics Data.Journal of proteome research · 2025Article
- Hypoxic stimulation of DCLK1 transcription and alternative-promoter switching fuels tumor malignancy in clear cell renal cell carcinoma.Cell death & disease · 2025Article
- Radiogenomic correlation of hypoxia-related biomarkers in clear cell renal cell carcinoma.Journal of cancer research and clinical oncology · 2025Article
- Topical transdermal administration of lenalidomide nanosuspensions-based hydrogels against melanoma: In vitro and in vivo studies.International journal of pharmaceutics: X · 2025Article
- Solute carrier protein family: physiological functions, disease associations, and therapeutic potential in immune-related disorders.Frontiers in immunology · 2025Review
- Prognostic biomarker and clinical significance of PLOD gene family in clear cell renal cell carcinoma.Frontiers in oncology · 2025Article
- E3 ubiquitin ligase TRIM2 identified as a novel suppressor of CYP11B2 and aldosterone production.Cellular and molecular life sciences : CMLS · 2024Article
- TDERS, an exosome RNA-derived signature predicts prognosis and immunotherapeutic response in clear cell renal cell cancer: a multicohort study.Journal of the National Cancer Center · 2024Article
- An Exogenous Ketone Ester Slows Tumor Progression in Murine Breast and Renal Cancer Models.Cancers · 2024Article
- Comprehensive investigation of malignant epithelial cell-related genes in clear cell renal cell carcinoma: development of a prognostic signature and exploration of tumor microenvironment interactions.Journal of translational medicine · 2024Article
- Targeting PLOD2 suppresses invasion and metastatic potential in radiorecurrent prostate cancer.BJC reports · 2024Article
- Celastrol Elicits Antitumor Effects through Inducing Immunogenic Cell Death and Downregulating PD-L1 in ccRCC.Current pharmaceutical design · 2024Article
- Immunotherapy and stereotactic body radiotherapy for older patients with non-metastatic renal cancer unfit for surgery or decline nephrectomy: practical proposal by the International Geriatric Radiotherapy Group.Frontiers in oncology · 2024Article
- Overexpression of Glycosyltransferase 8 Domain Containing 1 Promotes Gastric Cancer Proliferation and Inhibits Apoptosis via Mediating PTPN6/JAK2/STAT3 Signaling Axis.International journal of medical sciences · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Clear cell renal cell carcinoma (ccRCC) is a type of kidney cancer that is both common and aggressive, with a rising incidence in recent decades. Hypoxia is a key factor that plays a vital role in the tumorigenesis and metastasis of malignancy. However, the precise mechanisms of hypoxia driving ccRCC progression were not totally uncovered. Our study found that hypoxia level was elevated in ccRCC and might be an independent risk factor of prognosis in ccRCC patients. We identified a key protein PLOD2 was induced under hypoxic conditions and strongly associated with poor prognosis in ccRCC patients. When PLOD2 was depleted, the proliferation and migration of ccRCC cells were reduced in vitro and in vivo, while overexpression of PLOD2 had the opposite effect. Mechanically, the study further revealed that PLOD2 was transcriptionally activated by HIF1A, which binds to a specific promoter region of the PLOD2 gene. PLOD2 was also shown to interact with EGFR, leading to the phosphorylation of the receptor. Furthermore, PLOD2 was responsible for binding to the extracellular domain of EGFR, which ultimately activated the AKT signaling pathway, thus promoting the malignant progression of ccRCC. Treatment with the PLOD2 inhibitor Minoxidil significantly suppressed ccRCC progression by inactivating the EGFR/AKT signaling axis. In summary, the findings of this study shed light on the molecular mechanisms behind PLOD2 expression in ccRCC and suggest that it may serve as a potential predictor and therapeutic target for the clinical prognosis and treatment of ccRCC.
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