bims-meproc Biomed News
on Metabolism in Prostate Cancer
Issue of 2026–05–17
twelve papers selected by
Grigor Varuzhanyan, UCLA
  1. ADAMTS2 drives prostate cancer progression by activating FAK/PI3K/AKT signaling and suppressing ferroptosis via COL1A1.
  2. Histone lactylation modification promotes docetaxel resistance and tumor progression through CNN1-Mediated autophagy and cell cycle arrest in Castration-resistant prostate cancer.
  3. SRRT promotes prostate cancer progression and serves as a prognostic biomarker through STAT3 pathway activation.
  4. TLN1 interacts with NGFR and suppresses the development of castration-resistant prostate cancer by upregulating NGFR.
  5. F2R Promotes Prostate Cancer Progression via COL8A1-Dependent Activation of the FAK/PI3K/AKT Signaling Axis.
  6. CRLF1 Drives Prostate Cancer Progression via COMP-Mediated Activation of the FAK/PI3K/AKT Signaling Pathway.
  7. CBL proto-oncogene C-mediated synaptophysin 1 regulates prostate cancer progression in the TGF-beta signalling pathway.
  8. PARP1-BCAT2 axis upregulates ABCG1 via histone lactylation to drive acquired PARP inhibitor resistance in prostate cancer.
  9. Matrix and stromal cues cooperatively regulate dormancy-like states of prostate cancer in a dual-niche metastatic model.
  10. Lysine methyltransferase 5C (KMT5C) promoted malignant growth of prostate cancer through FGFR1/STAT3 pathway and regulated the immune response.
  11. USP29-regulated noncanonical stabilization of the hypoxia-inducible factor-α in aggressive prostate cancer.
  12. Metformin in Prostate Cancer: A Negative Repurposing Story Across the Disease Continuum.
  1. Front Oncol. 2026 ;16 1784882
    ADAMTS2 drives prostate cancer progression by activating FAK/PI3K/AKT signaling and suppressing ferroptosis via COL1A1.
    Jinzhuo Ning, Jinrun Wang, Lizhe Xu, Zhiyan Zhou, Haoyong Li.
       Background: ADAMTS2, a secreted metalloproteinase essential for collagen maturation, exhibits context-dependent roles in cancer but remains uncharacterized in prostate cancer (PCa). Its potential involvement in PCa progression and underlying mechanisms are unknown.
    Methods: We integrated bioinformatic analysis of TCGA-PRAD data with clinical specimen validation, in vitro functional assays (proliferation, migration, invasion), co-immunoprecipitation (Co-IP), ferroptosis sensitivity testing, pharmacological inhibition, and in vivo xenograft models to investigate ADAMTS2's expression, function, and molecular mechanisms in PCa.
    Results: ADAMTS2 was significantly upregulated in PCa tissues and cell lines, correlating with aggressive clinicopathological features and poor progression-free survival. Functionally, ADAMTS2 promoted PCa cell aggressiveness in vitro and tumor growth in vivo. Mechanistically, ADAMTS2 directly interacted with and upregulated COL1A1, leading to stimulation of the FAK/PI3K/AKT pathway. This cascade, in turn, enhanced the expression of ferroptosis defense proteins (SLC7A11 and GPX4), suppressed lipid peroxidation, and conferred resistance to ferroptosis. Pharmacological inhibition of FAK reversed both the oncogenic and anti-ferroptotic effects of ADAMTS2.
    Conclusions: Our investigation considers ADAMTS2 as a novel oncogenic driver in PCa that promotes tumor progression by reinforcing a tumor-permissive extracellular matrix through upregulation of COL1A1 and by stimulating the FAK/PI3K/AKT pathway to suppress ferroptosis. These findings position ADAMTS2 as a potential predictive biomarker and a valuable therapeutic target for defeating ferroptosis resistance in PCa.
    Keywords:  ADAMTS2; COL1A1; FAK/PI3K/AKT signaling; ferroptosis; prostate cancer
    DOI:  https://doi.org/10.3389/fonc.2026.1784882
  2. Cell Death Discov. 2026 May 13.
    Histone lactylation modification promotes docetaxel resistance and tumor progression through CNN1-Mediated autophagy and cell cycle arrest in Castration-resistant prostate cancer.
    Ruijie Mao, Xu Chen, Xing Fu, Dingyuan Yang, Wenqiang Chen, Jun Li.
      Castration-resistant prostate cancer (CRPC) constitutes an advanced stage of prostate cancer (PCa) that emerges following conventional androgen deprivation therapy (ADT). Docetaxel (DTX), a standard chemotherapeutic agent, is integral to the therapeutic regimen for CRPC. However, the development of resistance to DTX has significantly impeded its clinical efficacy. Histone lactylation and elevated lactate production are emerging as critical factors in cancer biology, yet their roles in CRPC and DTX resistance remain poorly understood. This study investigated the relationship between histone lactylation, lactate production, and DTX resistance in CRPC. Clinical analysis revealed significantly increased pan-lactylated protein (Pan Kla) expression in CRPC tissues compared to PCa, accompanied by elevated lactate production and lactate dehydrogenase (LDH) activity. Higher Pan Kla expression was linked to poor prognosis in CRPC. DTX-resistant CRPC (CRPC-R) samples exhibited significantly elevated Pan Kla and histone lactylation modifications, especially at H3K18la and H4K12la sites. Inhibition of lactate production using 2-deoxyglucose (2-DG) and oxamate reduced DTX resistance, suppressed cell migration, induced G0/G1 phase arrest, and promoted autophagy. Moreover, CNN1 was identified as a potential downstream target of histone lactylation modifications in CRPC. Elevated CNN1 expression correlated with increased lactylation and DTX resistance, whereas its inhibition reversed the effects of lactate inhibition on cell cycle progression and autophagy. In vivo, CNN1 overexpression counteracted the tumor-suppressive effects of lactate inhibition, restoring tumor growth and autophagy levels. These findings suggested that histone lactylation and lactate metabolism, mediated by CNN1, play a crucial role in DTX resistance and tumor progression in CRPC, offering potential therapeutic targets for overcoming chemoresistance in CRPC.
    DOI:  https://doi.org/10.1038/s41420-026-03141-8
  3. Oncol Rep. 2026 Jul;pii: 129. [Epub ahead of print]56(1):
    SRRT promotes prostate cancer progression and serves as a prognostic biomarker through STAT3 pathway activation.
    Lingxiang Lu, Ke Wu, Zhenfan Wang, Ruoxi Yang, Kai Li, Shuai Guo, Fei Wang, Zheng Ma.
      Prostate cancer (PC) is a highly prevalent malignancy in men with substantial prognostic heterogeneity. The present study aimed to identify novel prognostic biomarkers and investigate their functional roles and underlying mechanisms in PC. To this end, integrated bioinformatics analyses were performed using The Cancer Genome Atlas‑prostate adenocarcinoma cohort and two Gene Expression Omnibus datasets. A total of 95 common differentially expressed genes were identified and were significantly enriched in the STAT3 signaling pathway. Lasso and Cox regression analyses screened nine independent prognostic genes, among which SRRT exhibited the highest risk coefficient. The constructed risk model showed strong predictive performance for disease‑free survival and favorable calibration in nomogram analysis. Experimental validation demonstrated that SRRT was markedly upregulated in PC tissues and cell lines, and functional assays revealed that SRRT knockdown inhibited, whereas overexpression promoted, proliferation and migration of DU145 and PC‑3 cells in vitro and tumor growth in vivo. Mechanistically, SRRT enhanced STAT3 phosphorylation, and activation of STAT3 by colivelin partially reversed the suppressive effects of SRRT silencing, indicating that SRRT promotes PC progression through activation of the STAT3 signaling pathway. Collectively, SRRT acts as an independent adverse prognostic biomarker that promotes PC progression, and the present findings provide integrated bioinformatic and experimental evidence linking SRRT to STAT3 pathway activation.
    Keywords:  SRRT; STAT3 signaling pathway; biomarker; prostate adenocarcinoma
    DOI:  https://doi.org/10.3892/or.2026.9134
  4. Front Immunol. 2026 ;17 1802129
    TLN1 interacts with NGFR and suppresses the development of castration-resistant prostate cancer by upregulating NGFR.
    Sixin Li, Anjie Chen, Chen Guo, Chenwei Gu, Zhonghao Tang, Si Shen, Dongjie Yang, Yuanyuan Mi.
       Background: Prostate cancer (PCa) is a common malignant tumor in males, and castration-resistant prostate cancer (CRPC) represents an advanced stage with limited treatment options and poor prognosis. Talin-1 (TLN1) is a cytoskeletal protein implicated in tumor progression, but its specific role and mechanism in CRPC remain unclear.
    Methods: Mass spectrometry (MS) was used to analyze serum peptides from patients with hormone-sensitive prostate cancer (HSPC) and CRPC. TLN1 expression was further validated in clinical prostate tissue samples (59 PCa, 17 benign prostatic hyperplasia) via immunohistochemistry, qPCR, and Western blot. Functional assays (CCK-8, colony formation, wound healing, Transwell) and a nude mouse xenograft model were employed to assess the effects of TLN1 knockdown on CRPC cell lines (DU145, PC3). Transcriptome sequencing, molecular docking, and co-immunoprecipitation (Co-IP) were conducted to explore downstream mechanisms and interactions. Western blot analysis was applied to examine the impact of TLN1 knockdown on apoptosis and the PI3K-AKT, MAPK, and NF-κB signaling pathways in CRPC cell lines. Rescue experiments were performed by knocking down both TLN1 and nerve growth factor receptor (NGFR).
    Results: TLN1 expression was significantly upregulated in CRPC patient serum and PCa tissues. Knockdown of TLN1 inhibited proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), promoted apoptosis in CRPC cells, and suppressed tumor growth in vivo. Transcriptome analysis identified NGFR as significantly upregulated upon TLN1 knockdown. TLN1 knockdown can influence the malignant progression of CRPC through the MAPK and PI3K-AKT signaling pathways. Molecular docking and Co-IP confirmed a direct interaction between TLN1 and NGFR. Knockdown of NGFR reversed the tumor-suppressive effects induced by TLN1 silencing.
    Conclusions: TLN1 inhibits the progression of CRPC by interacting with and regulating the tumor suppressor NGFR. The TLN1/NGFR axis represents a novel potential therapeutic target for CRPC.
    Keywords:  NGFR; TLN1; castration-resistant prostate cancer; prostate cancer; therapeutic target
    DOI:  https://doi.org/10.3389/fimmu.2026.1802129
  5. J Gene Med. 2026 May;28(5): e70097
    F2R Promotes Prostate Cancer Progression via COL8A1-Dependent Activation of the FAK/PI3K/AKT Signaling Axis.
    Xianfan Ding, Jinrun Wang, Jinzhuo Ning, Haoyong Li, Fan Cheng.
       BACKGROUND: In males, prostate cancer (PCa) is one of the frequently diagnosed forms of cancer, with high clinical variability and limited treatment options for advanced cases. This receptor, which goes by the names Coagulation Factor II Receptor (F2R) and PAR1, belongs to the family of G-protein-linked membrane proteins and plays roles in both blood clotting processes and the development of malignancies. Whereas F2R has been associated with tumor progression in various malignancies, its specific involvement in PCa is not well understood. Here, we seek to examine the expression patterns and biological functions of F2R to better understand its impact on PCa progression.
    METHODS: We systematically analyzed F2R expression in PCa using data from the TCGA database and clinical specimens. Functional experiments, including cell proliferation, invasion, and apoptosis assays, were conducted in PCa cell lines with F2R overexpression or knockdown. Bioinformatics analyses were performed to identify F2R-associated genes and signaling pathways. In vivo xenograft models were used to validate the oncogenic role of F2R.
    RESULTS: Our results demonstrated that F2R is significantly overexpressed in PCa tissues and correlates with advanced clinicopathological features such as higher T stage, nodal metastasis, and elevated Gleason scores. Functional studies revealed that F2R promotes PCa cell proliferation, invasion, and cell cycle progression while inhibiting apoptosis. Mechanistically, we identified collagen type VIII alpha 1 (COL8A1) as a key downstream effector of F2R, which activates the FAK/PI3K/AKT signaling pathway. In vivo experiments confirmed that F2R knockdown suppresses tumor growth and downregulates this signaling axis.
    CONCLUSION: This study highlights F2R as an important promoter in PCa progression and identifies the F2R-COL8A1-FAK/PI3K/AKT signaling axis as a potential molecular mechanism underlying tumor aggressiveness.
    Keywords:  COL8A1; F2R; FAK/PI3K/AKT pathway; PCa
    DOI:  https://doi.org/10.1002/jgm.70097
  6. Cancers (Basel). 2026 Apr 28. pii: 1395. [Epub ahead of print]18(9):
    CRLF1 Drives Prostate Cancer Progression via COMP-Mediated Activation of the FAK/PI3K/AKT Signaling Pathway.
    Zhongze Li, Jinrun Wang, Lizhe Xu, Jinzhuo Ning, Fan Cheng.
      Background: Cytokine-like receptor family 1 (CRLF1) has been implicated in tumor progression, yet its prognostic function and mechanistic actions in prostate cancer (PCa) remain elusive. Objective: This investigation sought to clarify the functional role, molecular mechanisms, and clinical relevance of CRLF1 in the progression of PCa. Methods: We conducted extensive bioinformatics analyses utilizing the protein interaction networks and the TCGA-PRAD dataset. CRLF1 and cartilage oligomeric matrix protein (COMP) expression were validated in clinical samples by qRT-PCR and Western blot (WB). Functional assessments, including Transwell invasion, flow cytometry, CCK-8, and wound healing, were conducted in vitro. An in vivo xenograft tumor model was used for further validation. Mechanistic investigations involved genetic perturbation (overexpression and inhibition) of CRLF1 and COMP. Results: Compared to benign tissues, the levels of CRLF1 and COMP were markedly elevated in PCa tissues. Bioinformatics assessments illustrated a robust positive relationship between CRLF1 and COMP, suggesting COMP may function as a downstream mediator. In vitro and in vivo investigations illustrated that silencing CRLF1 significantly suppressed PCa cell growth, invasion, and tumor progression, while enhancing apoptosis. Importantly, suppressing COMP counteracted the cancer-promoting effects triggered by CRLF1 overexpression. At the mechanistic level, CRLF1 facilitates tumor progression by modulating COMP to activate the FAK/PI3K/AKT signaling cascade. Conclusions: Our outcomes demonstrate that CRLF1 promotes PCa progression by targeting COMP to stimulate the FAK/PI3K/AKT signaling axis. This newly identified CRLF1/COMP/FAK/PI3K/AKT pathway underscores CRLF1 as a potential biomarker and therapeutic target for PCa.
    Keywords:  COMP; CRLF1; PCa; biomarker; tumor progression
    DOI:  https://doi.org/10.3390/cancers18091395
  7. Mol Immunol. 2026 May 12. pii: S0161-5890(26)00111-2. [Epub ahead of print]195 117-129
    CBL proto-oncogene C-mediated synaptophysin 1 regulates prostate cancer progression in the TGF-beta signalling pathway.
    Jianyong Tong, Liang Hu, Quanqi Liu, Daxue Tian.
       OBJECTIVE: This study aims to screen and validate the differentially expressed gene synaptophysin 1 (SYT1), which plays a key regulatory role in prostate cancer, explore its function and potential regulatory mechanisms, and clarify its biological role and molecular mechanisms in the malignant progression of prostate cancer.
    METHODS: Differential expression analysis was performed using the GEO database dataset GSE69223, combined with the TIMER and UALCAN databases to validate the expression levels and prognostic value of the candidate gene SYT1. To further ensure the biological plausibility of the results, this study selected cell lines representing different prostate cancer subtypes and disease stages, including the normal epithelial cell line RWPE-1, the adenocarcinoma-like AR⁺ cell line LNCaP, the basal-like/AR⁻ cell line PC3, and the neuroendocrine cell line NCI-H660, and assessed differences in SYT1 expression using qRT-PCR and Western blot analysis. SYT1-overexpressing cell lines were established, and their effects on prostate cancer cell proliferation, migration, and invasion were assessed using EDU, colony formation, scratch, and Transwell assays. Using UbiBrowser, we predicted potential E3 ubiquitin ligases for SYT1 and screened CBL proto-oncogene C (CBLC) as a candidate upstream regulatory factor through differential analysis. We validated the regulatory role of CBLC in SYT1 ubiquitination and degradation via immunoprecipitation experiments and explored its mechanism of action through functional interaction experiments and signalling pathway analysis.
    RESULTS: SYT1 is significantly downregulated in prostate cancer tissues, and its downregulation is associated with poor prognosis in prostate cancer. Overexpression of SYT1 significantly inhibits the proliferation, migration, and invasion of prostate cancer cells. CBLC is highly expressed in prostate cancer and promotes the ubiquitination and degradation of SYT1. Knocking down CBLC reduces the ubiquitination level of SYT1 and stabilises its protein expression. Overexpression of CBLC partially reverses the antitumour effects mediated by SYT1. Mechanistic studies indicate that SYT1 exerts its antitumour function by inhibiting the TGF-β/SMAD signalling pathway, while CBLC interferes with this pathway by promoting its degradation.
    CONCLUSION: Prostate cancer may have SYT1 as a tumor suppressor gene, and the E3 ligase CBLC regulates its ubiquitin-mediated degradation. SYT1 inhibits tumour progression by suppressing the TGF-β/SMAD signalling pathway, while CBLC promotes the malignant development of prostate cancer by negatively regulating SYT1.
    Keywords:  CBL proto-oncogene C; Prostate cancer; Synaptotagmin 1; Transforming growth factor-beta signalling pathway
    DOI:  https://doi.org/10.1016/j.molimm.2026.04.019
  8. J Exp Clin Cancer Res. 2026 May 11.
    PARP1-BCAT2 axis upregulates ABCG1 via histone lactylation to drive acquired PARP inhibitor resistance in prostate cancer.
    Wangli Mei, Hang Zhou, Weiyi Li, Yongqiang Liu, Chaozhi Tang, Mengyu Wei, Zhen Zhou, Bowen Ye, Hanwen Niu, Weitian Wang, Kaiqi Yang, Yue Zhang, Liqun Huang, Yang Yu, Xiaofei Wen, Lin Ye.
       BACKGROUND: Poly (ADP-ribose) polymerase inhibitor (PARPi) resistance poses a significant challenge in prostate cancer (PCa). Although branched-chain amino acid (BCAA) metabolism is implicated in cancer biology, its specific role in PARPi resistance remains unclear. This study aims to investigate how BCAA metabolism contributes to PARPi resistance in PCa.
    METHODS: We compared BCAA and Branched-Chain Amino Acid Aminotransferase 2 (BCAT2) levels between PARPi-resistant and PARPi-sensitive cell lines and assessed their clinical relevance. Functional studies were conducted in vitro and in vivo using cell and mouse models. Mechanistic assays, including RNA sequencing, metabolomics, RNA-binding protein immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and Cleavage Under Targets and Tagmentation (CUT&Tag), were used to delineate BCAT2-mediated PARPi resistance.
    RESULTS: BCAT2 expression correlated with PARPi resistance in PCa, and increased BCAA/BCAT2 levels in PARPi-resistant tissues were associated with reduced patient survival. Mechanistically, the DNA-binding domain (DBD) of PARP1 directly bound BCAT2 mRNA and regulated its stability; PARPi-induced PARP1 trapping weakened this interaction, increased BCAT2 expression, and promoted resistance. Transcriptomic and energy-metabolism analyses indicated that BCAT2 enhanced ABCG1 transcription by augmenting glycolysis and lactate secretion, thereby increasing histone H3K18la lactylation. These findings support a PARP1-BCAT2-ABCG1 axis in PARPi resistance. Combining a BCAT2 inhibitor with PARPi produced synergistic effects in cell line-derived xenografts (CDXs) and patient-derived organoids (PDOs).
    CONCLUSION: The PARP1-BCAT2/H3K18la-ABCG1 axis drives PARPi resistance in PCa. Targeted BCAT2 inhibition may enhance the therapeutic efficacy of PARPi.
    Keywords:  ABCG1; BCAT2; Lactylation; PARP1; PARPi resistance; Prostate cancer
    DOI:  https://doi.org/10.1186/s13046-026-03719-1
  9. Clin Exp Metastasis. 2026 May 16. pii: 26. [Epub ahead of print]43(3):
    Matrix and stromal cues cooperatively regulate dormancy-like states of prostate cancer in a dual-niche metastatic model.
    Bo Han, Zhi Yang, Shuqing Zhao, Gangning Liang, Ba Xuan Hoang.
      Prostate cancer (PCa) exhibits a strong tropism for bone, where interactions with the bone microenvironment critically influence metastatic progression and therapeutic resistance. However, the complexity of tumor-bone interactions remains difficult to model in conventional systems. Here, we developed an engineered dual-niche platform that recapitulates both primary tumor and bone metastatic microenvironments using tunable extracellular matrix mechanics, bone matrix-derived soluble factors (BMSFs), and bone marrow stromal cells (BMSCs). Within the primary tumor-like niche, increasing matrix stiffness suppressed LNCaP-C4-2B cell proliferation while promoting cell dissemination. In contrast, BMSFs exerted a dual effect by inhibiting tumor proliferation while inducing osteomimetic differentiation through upregulation of Runx2 and Cbfa1. In vivo, BMSFs elicited inflammatory and vascular responses associated with suppressed tumor expansion. Notably, BMSCs primed with bone matrix factors markedly enhanced PCa cell proliferation and migration in vitro and accelerated tumor formation in vivo, revealing a stromal-driven pro-tumorigenic mechanism. Together, these findings uncover a functional dichotomy within the bone microenvironment, in which bone matrix-derived factors promote tumor adaptation and dormancy, while stromal components drive tumor expansion. This engineered dual-niche model provides a versatile platform to dissect microenvironment-specific mechanisms and may inform strategies targeting bone metastatic progression in prostate cancer.
    Keywords:  Bone marrow stromal cells; Bone metastasis; Osteomimicry; Prostate cancer; Tumor dormancy; Tumor microenvironment
    DOI:  https://doi.org/10.1007/s10585-026-10405-1
  10. Cell Signal. 2026 May 13. pii: S0898-6568(26)00253-6. [Epub ahead of print] 112600
    Lysine methyltransferase 5C (KMT5C) promoted malignant growth of prostate cancer through FGFR1/STAT3 pathway and regulated the immune response.
    Shuhang Li, Lechao Zhang, Peng Yu.
       BACKGROUND: The role of KMT5C varies across different tumor types, while its expression and function in prostate cancer remain largely unreported. This study investigated KMT5C expression in prostate cancer and its effects on tumor growth and immune response.
    METHODS: Following KMT5C knockdown and overexpression, we evaluated cell proliferation, cell cycle distribution and angiogenesis, and detected the activation of FGFR1/STAT3 pathway via Western blot. The molecular interaction between KMT5C and FGFR1 was bioinformatically predicted and experimentally validated. Subcutaneous xenograft models in nude and C57BL/6 mice were constructed to explore the effects of KMT5C on prostate cancer progression and tumor immune regulation.
    RESULT: Our findings showed that KMT5C was highly expressed in prostate cancer and functions as an oncogene to facilitate cell proliferation, angiogenesis, and G0/G1-to-S cell cycle transition. Conversely, KMT5C knockdown suppressed cell proliferation, angiogenesis and arrested the G0/G1/S phase transition. Mechanistically, the oncogenic properties of KMT5C were partially dependent on the activation of FGFR1/STAT3 signaling pathway. KMT5C depletion increased the proportion of CD8+ T cells in the spleen and elevated the infiltration of CD8+ cytotoxic T lymphocytes within the tumor microenvironment.. Moreover, KMT5C silencing induced the polarization of tumor-associated macrophages (TAMs) from the M2-like immunosuppressive phenotype to the M1-like anti-tumor phenotype.
    CONCLUSION: KMT5C acts as a critical oncogenic driver in prostate cancer, which is closely associated with tumor malignancy and tumor immune homeostasis. Thus, KMT5C may serve as a promising therapeutic target for prostate cancer intervention. Collectively, our findings provide solid experimental evidence for the clinical relevance of KMT5C.
    Keywords:  FGFR1/STAT3 pathway; Immune response; Lysine methyltransferase 5C; Prostate cancer
    DOI:  https://doi.org/10.1016/j.cellsig.2026.112600
  11. Mol Oncol. 2026 May 13.
    USP29-regulated noncanonical stabilization of the hypoxia-inducible factor-α in aggressive prostate cancer.
    Amelie S Schober, Leire Moreno-Cugnon, Laura Martínez-Pérez, Amaia Ercilla, Amaia Zabala-Letona, Adrián Vicente-Barrueco, Maider Fagoaga-Eugui, Saioa Garcia-Longarte, Blanca Calle-Ciborro, Encarnación Pérez-Andrés, Onintza Carlevaris, Sara Pozo, Isabel Mendizabal, Ugo Mayor, Arkaitz Carracedo, Violaine Sée, Edurne Berra.
      Oxygen availability is frequently compromised in solid tumours, making intratumoural hypoxia a common feature of cancer. In prostate cancer (PCa), hypoxia is strongly associated with aggressive disease and poor prognosis. Hypoxia-inducible factor (HIF) is the master transcriptional regulator mediating hypoxia adaptation and is mainly controlled through proteasomal degradation of its α-subunit by the ubiquitin-proteasome system (UPS). However, the contribution of deubiquitinases (DUBs) to HIF signalling in PCa remains largely unexplored. Using a computational strategy based on CA9 expression as a surrogate of HIF activity, we identified Ubiquitin-Specific Protease 29 (USP29) as a key regulator associated with hypoxia and tumour progression and severity in PCa. Mechanistically, USP29 functions as a noncanonical positive regulator of HIF-α stability in a catalytic-dependent manner. USP29 interacts with HIF-1α, reduces its poly-ubiquitination and protects it from proteasomal degradation across multiple cancer cell lines. Additionally, USP29 stabilizes HIF-2α acting on the C-terminal region of HIF-α. These findings uncover a novel regulatory layer of HIF signalling and highlight USP29 as a potential therapeutic target in hypoxia-driven PCa progression.
    Keywords:  HIF; USP29; deubiquitinases; hypoxia; prostate cancer
    DOI:  https://doi.org/10.1002/1878-0261.70268
  12. Eur Urol Oncol. 2026 May 08. pii: S2588-9311(26)00123-9. [Epub ahead of print]
    Metformin in Prostate Cancer: A Negative Repurposing Story Across the Disease Continuum.
    Dries Develtere, Gaëtan Devos.
      
    DOI:  https://doi.org/10.1016/j.euo.2026.04.014
This page is being maintained by Thomas Krichel. It was last updated on 2026‒06‒01 at 2:02.