ArticleOncogene2020
EGFR-upregulated LIFR promotes SUCLG2-dependent castration resistance and neuroendocrine differentiation of prostate cancer.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 38 citations in OpenAlex.
- SUCLG2 contributes to platinum resistance in lung adenocarcinoma through enhancing succinylation of GAC and glutamine metabolism.Apoptosis : an international journal on programmed cell death · 2026Article
- Co-targeting EGFR and SUCLG2 disrupts a nuclear transcriptional program driving neuroendocrine differentiation and TKI resistance in castration-resistant prostate cancer.Cell communication and signaling : CCS · 2026Article
- Extracellular Domain Shedding of TROP2 Activates EGFR Signaling to Drive Prostate Cancer Metastasis.Cancer research · 2025Article
- CircPSD3 aggravates tumor progression by maintaining TCA cycle and mitochondrial function via regulating SUCLG2 in thyroid carcinoma.Cell death & disease · 2025Article
- Metabolism-Related Genes SMOX and SUCLG2 as Immunological and Prognostic Biomarkers in Colorectal Cancer: A Pan-Cancer Analysis.Current issues in molecular biology · 2025Article
- Exploring the prognostic significance and therapeutic potential of SUCLG2 in prostate cancer.Frontiers in genetics · 2025Article
- Machine learning based predictive model and genetic mutation landscape for high-grade colorectal neuroendocrine carcinoma: a SEER database analysis with external validation.Frontiers in oncology · 2025Article
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- Review
- Understanding the function of Pax5 in development of docetaxel-resistant neuroendocrine-like prostate cancers.Cell death & disease · 2024Article
- Article
- Immunosuppressive role of BDNF in therapy-induced neuroendocrine prostate cancer.Molecular oncology · 2024Article
- Molecular landscape for risk prediction and personalized therapeutics of castration-resistant prostate cancer: at a glance.Frontiers in endocrinology · 2024Review
- Understanding the role of Pax5 in development of taxane-resistant neuroendocrine like prostate cancers.Research square · 2023Article
- SUCLG2 Regulates Mitochondrial Dysfunction through Succinylation in Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Genetics of enzymatic dysfunctions in metabolic disorders and cancer.Frontiers in oncology · 2023Review
- Label-Free Quantitative Proteomics Analysis of Adriamycin Selected Multidrug Resistant Human Lung Cancer Cells.Biomolecules · 2022Article
- Molecular mechanisms of neuroendocrine differentiation in prostate cancer progression.Journal of cancer research and clinical oncology · 2022Review
- Targeting LIF/LIFR signaling in cancer.Genes & diseases · 2022Review
- The Pleiotropic role, functions and targeted therapies of LIF/LIFR axis in cancer: Old spectacles with new insights.Biochimica et biophysica acta. Reviews on cancer · 2022Review
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroendocrine (NE) differentiation is a well-recognized phenotypic change of prostate cancer after androgen deprivation therapy (ADT), and it ultimately develops into an aggressive subset of this disease. However, the contribution of signaling pathways that lead to metabolic disorders and NE differentiation of prostate cancer remains unclear. In this study, we identified that ADT induced upregulation of the succinate-CoA ligase GDP-forming beta subunit (SUCLG2), which regulates succinate metabolism and NE differentiation of prostate cancer. We demonstrated a connection that upregulation of epidermal growth factor receptor (EGFR)-leukemia inhibitory factor receptor (LIFR) signaling induced SUCLG2 expression in prostate cancer cells. The LIFR is upregulated by nuclear EGFR, which acts as a transcriptional regulator, directly binds to the LIFR promoter, and drives NE differentiation and glycolysis of prostate cancer. LIFR upregulation is associated with SUCLG2, which increased succinate synthesis and enzymatic activities of mitochondrial nucleoside diphosphate kinase (NDPK) in prostate cancer cells. Knockdown of SUCLG2 suppressed NE differentiation in cultured cells and reduced prostate tumor growth in a xenograft model. Analysis of prostate tissue samples showed increased intensity of nuclear EGFR associated with the LIFR and SUCLG2 in castration-resistant prostate cancer tumors. Our study provides a mechanism whereby ADT upregulates EGFR-LIFR signaling that activates SUCLG2, which subsequently stimulates the metabolic changes associated with NE differentiation and aggressive prostate cancer phenotype.
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