The pathogenesis and therapeutic implications of metabolic reprogramming in renal cell carcinoma DOI Creative Commons
Yifan Zhang, Shengli Zhang, Hongbin Sun

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 19, 2025

Abstract Renal cell carcinoma (RCC), a therapeutically recalcitrant genitourinary malignancy, exemplifies the profound interplay between oncogenic signaling and metabolic adaptation. Emerging evidence positions reprogramming as central axis of RCC pathogenesis, characterized by dynamic shifts in nutrient utilization that transcend canonical Warburg physiology to encompass lipid anabolism, glutamine auxotrophy, microenvironment-driven plasticity. This orchestrated rewiring cellular energetics sustains tumor proliferation under hypoxia while fostering immunosuppression through metabolite-mediated T exhaustion myeloid-derived suppressor activation. Crucially, exhibits heterogeneity across histological subtypes intratumoral regions—a feature increasingly recognized determinant therapeutic resistance. Our review systematically deciphers molecular architecture metabolism, elucidating how VHL/HIF mutations, mTOR pathway dysregulation, epigenetic modifiers converge reshape glucose flux, droplet biogenesis, amino acid catabolism. We present novel insights into spatial zonation within tumors, where pseudohypoxic niches engage lactate shuttling cholesterol efflux adjacent vasculature, creating pro-angiogenic immunosuppressive microdomains. Therapeutically, we evaluate first-in-class inhibitors targeting rate-limiting enzymes de novo lipogenesis proposing biomarker-driven strategies overcome compensatory highlight synergy glutaminase PD-1 blockade reinvigorating CD8 + function, role lipid-loaded cancer-associated fibroblasts shielding tumors from ferroptosis. Finally, outline translational roadmap integrating multi-omics profiling, functional metabolomics, biology match vulnerabilities with precision therapies.

Language: Английский

The p-MYH9/USP22/HIF-1α axis promotes lenvatinib resistance and cancer stemness in hepatocellular carcinoma DOI Creative Commons

Qiaonan Shan,

Lu Yin,

Qifan Zhan

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 19, 2024

Language: Английский

Citations

5
Molecular mechanisms of renal cell carcinoma metastasis and potential targets for therapy DOI Creative Commons
Xinwei Li, Wei Xiong,

Zhiyong Xiong

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 20, 2025

Renal cell carcinoma is a common type of cancer, with approximately 30% patients potentially developing metastatic disease. Some renal are found in advanced stages, so the 5-year survival rate for only 14%. Currently, there several drugs available carcinoma, and their overall can be extended to nearly 5 years. However, sensitivity efficacy treatment still unsatisfactory. New targets improve patient prognosis urgently needed, but these closely linked molecular mechanisms metastasis. In this review, we present definition provide new insights on potential link targeted therapies, which may enlighten scientists develop future therapeutic agents carcinoma.

Language: Английский

Citations

0
CRYAB is upregulated and predicts clinical prognosis in kidney renal clear cell carcinoma DOI
Hao Ren, Xinyu Chen,

Meiling Ji

et al.

IUBMB Life, Journal Year: 2025, Volume and Issue: 77(1)

Published: Jan. 1, 2025

Abstract Clear cell renal carcinoma (KIRC) is the most prevalent subtype of (RCC), accounting for 70% to 80% all RCC cases. The CRYAB (αB‐crystallin) gene broadly expressed across various human tissues, yet its role in KIRC progression remains unclear. This study aims elucidate function and assess potential as a biomarker early diagnosis, therapeutic targeting, prognosis. In our report, we found that was dramatically upregulated KIRC, expression associated with TNM stage, pathological age. Also, patients higher exhibited poor survival overexpression led enhanced tumor proliferation. Vice versa, downregulation resulted decreased proliferation vitro. Mechanistically, Gene set enrichment analysis plots showed survival. Consistently, these effects were increased AKT signaling BCL‐2 expression. Furthermore, also observed levels negatively correlated immunocyte infiltration. conclusion, findings suggested could be regarded latent

Language: Английский

Citations

0
ESM1 promote proliferation, invasion and angiogenesis via Akt/mTOR and Ras pathway in kidney renal clear cell carcinoma DOI Creative Commons
Jianjun Luo, Ting Yi, Yong Wang

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 10, 2025

The most common types of renal carcinoma is kidney clear cell (KIRC). ESM1 a secreted protein, which involved in, lipids and glucose metabolism, but their role in angiogenesis contradictory different disease, especially KIRC. Bioinformatic analysis confirmed the expression prognosis IHC staining revealed protein KIRC samples. proliferation migration were tested by MTT, EdU, transwell analysis. its paracrine function was functional experiments. downstream molecular mechanism further elucidated WB significantly increased with prognostic significance. knockdown inhibited invasiveness capability viability cell. enhanced HUVECs to format tube conditional medium. induced inactivation Akt/mTOR Ras pathway attenuate proliferation, migration, invasion key tumor microenvironment (TME) KIRC, promoted invasion, activating pathway. It potential therapeutic target for patients.

Language: Английский

Citations

0
The human 18S rRNA m6A methyltransferase METTL5 promotes tumorigenesis via DEPDC1 in lung squamous cell carcinoma DOI Creative Commons
Yan Yang, Jianjun Fu

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 13, 2025

Background N6-Methyladenosine (m6A) is one of the post-transcriptional modifications and abnormal m6A critical for cancer initiation, progression, metastasis in Lung squamous cell carcinoma (LUSC). Ribosomal RNA (rRNA) accounts most total cellular RNA, however, functions molecular mechanisms underlying rRNA LUSC remained largely unclear. Methods High-throughput library screening identifies key regulator METTL5 LUSC. Cell animal experiments were used to identify that promoted tumorigenesis enhance DEP domain containing 1 (DEPDC1) translation via modification. Results We showed N6-methyladenosine methyltransferase was an independent risk factor associated with poor prognosis patients. Notedly, overexpression modification, while knockdown markedly inhibited proliferation migratory ability tumor cells vitro vivo . Mechanistically, m6a increase DEPDC1. Conclusion Our results revealed enhances DEPDC1 contribute prognosis, providing a potential prognostic biomarker therapeutic target

Language: Английский

Citations

0
The pathogenesis and therapeutic implications of metabolic reprogramming in renal cell carcinoma DOI Creative Commons
Yifan Zhang, Shengli Zhang, Hongbin Sun

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 19, 2025

Abstract Renal cell carcinoma (RCC), a therapeutically recalcitrant genitourinary malignancy, exemplifies the profound interplay between oncogenic signaling and metabolic adaptation. Emerging evidence positions reprogramming as central axis of RCC pathogenesis, characterized by dynamic shifts in nutrient utilization that transcend canonical Warburg physiology to encompass lipid anabolism, glutamine auxotrophy, microenvironment-driven plasticity. This orchestrated rewiring cellular energetics sustains tumor proliferation under hypoxia while fostering immunosuppression through metabolite-mediated T exhaustion myeloid-derived suppressor activation. Crucially, exhibits heterogeneity across histological subtypes intratumoral regions—a feature increasingly recognized determinant therapeutic resistance. Our review systematically deciphers molecular architecture metabolism, elucidating how VHL/HIF mutations, mTOR pathway dysregulation, epigenetic modifiers converge reshape glucose flux, droplet biogenesis, amino acid catabolism. We present novel insights into spatial zonation within tumors, where pseudohypoxic niches engage lactate shuttling cholesterol efflux adjacent vasculature, creating pro-angiogenic immunosuppressive microdomains. Therapeutically, we evaluate first-in-class inhibitors targeting rate-limiting enzymes de novo lipogenesis proposing biomarker-driven strategies overcome compensatory highlight synergy glutaminase PD-1 blockade reinvigorating CD8 + function, role lipid-loaded cancer-associated fibroblasts shielding tumors from ferroptosis. Finally, outline translational roadmap integrating multi-omics profiling, functional metabolomics, biology match vulnerabilities with precision therapies.

Language: Английский

Citations

0