Biochimica et biophysica acta. Molecular cell research最新文献_第3页

The endocytic fission protein EHD1 interacts with tubulin and regulates microtubule function 内吞裂变蛋白EHD1与微管蛋白相互作用并调节微管功能。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2026-01-27 DOI: 10.1016/j.bbamcr.2026.120120

Bazella Ashraf , Journey Reddick-Umoja , Jasmyn Grant , Jyoti Iyer , Naava Naslavsky , Steve Caplan

{"title":"The endocytic fission protein EHD1 interacts with tubulin and regulates microtubule function","authors":"Bazella Ashraf , Journey Reddick-Umoja , Jasmyn Grant , Jyoti Iyer , Naava Naslavsky , Steve Caplan","doi":"10.1016/j.bbamcr.2026.120120","DOIUrl":"10.1016/j.bbamcr.2026.120120","url":null,"abstract":"<div><div>The Eps15 Homology Domain protein-1 (EHD1) is an ATPase and key endocytic regulatory protein required for optimal receptor recycling, and primary ciliogenesis. Over the past decade, a central role for EHD1 has been identified in the fission of endosomes. Despite these findings, additional evidence has also pointed at a potential function of EHD1 in the regulation of microtubules. Herein, we demonstrate that EHD1 regulates the distribution of endosomes, and conversely, centrosome depletion alters EHD1 localization in cells. We show that endogenous EHD1 is found in a complex with various endogenous tubulins including TUBB3, TUBB1, α-tubulin and γ-tubulin, interactions that are independent of intact microtubules, and appear to be indirect. Depletion of key individual EHD1 interaction partners that are known to bind tubulin fail to impede EHD1-tubulin interactions, suggesting that either several proteins are capable of mediating EHD1's connection with microtubules, or that the bridging interaction partner remains to be identified. Functionally, EHD1 depletion leads to impaired microtubule regrowth and decreased end-binding protein displacement, suggesting a role for EHD1 in modulating microtubule plus-end dynamics. Finally, EHD1's role in microtubule regulation appears to be evolutionarily conserved, as single-cell stage <em>C. elegans</em> embryos with a dysfunctional EHD1/RME-1 protein displayed enhanced tubulin accumulation at metaphase spindle poles. Our findings strongly support a previously unaddressed role for EHD1 in microtubule regulation.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120120"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146083933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FOXA2/ALDOB axis modulation of fatty acid beta-oxidation influences irinotecan resistance in colorectal cancer FOXA2/ALDOB轴调控脂肪酸β -氧化影响结直肠癌患者伊立替康耐药

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2026-01-07 DOI: 10.1016/j.bbamcr.2026.120108

Yuan Jin , Chao Hu , Dianfu Pang

{"title":"FOXA2/ALDOB axis modulation of fatty acid beta-oxidation influences irinotecan resistance in colorectal cancer","authors":"Yuan Jin , Chao Hu , Dianfu Pang","doi":"10.1016/j.bbamcr.2026.120108","DOIUrl":"10.1016/j.bbamcr.2026.120108","url":null,"abstract":"<div><div>Colorectal cancer (CRC) exhibits altered lipid metabolism associated with therapy resistance. FOXA2, a lipid metabolism activator, mediates fatty acid β-oxidation in CRC, but its role in irinotecan (CPT-11) resistance remains unclear. Through bioinformatics analysis, clinical sample assessment, and cell line validation, we confirmed the expression of FOXA2 in CRC. The impact of FOXA2 on the viability and CPT-11 sensitivity of CRC cells was tested <em>via</em> CCK-8 assay. DNA damage was evaluated using the comet assay and monitoring of γ-H2AX foci. Assay kits determined the concentrations of triglycerides, cholesterol, and phospholipids, as well as the rate of fatty acid β-oxidation. Protein expression related to lipid metabolism (ACLY, SCD1) was identified by WB. Bioinformatic tools were used to analyze the potential transcriptional control of Aldolase B (ALDOB) by <em>FOXA2</em> and to scrutinize <em>ALDOB</em> expression in CRC. The molecular interaction was substantiated by dual-luciferase and CHIP assays. IHC was performed on an xenograft tumor model in mice to measure FOXA2, ALDOB, and Ki67 expression. Oil Red O staining was applied to detect triglyceride presence, and TUNEL was used to gauge apoptosis. The results showed that FOXA2 overexpression correlated with CPT-11 resistance in CRC. FOXA2 transcriptionally activated ALDOB, enhancing fatty acid β-oxidation and suppressing drug sensitivity. FOXA2 inhibition sensitized CRC cells to CPT-11 <em>in vitro</em>/vivo, while ALDOB overexpression restored resistance. These findings indicate that FOXA2 promotes CPT-11 resistance by upregulating ALDOB-mediated fatty acid β-oxidation. Targeting the FOXA2/ALDOB axis may overcome chemoresistance in CRC.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120108"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145942380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Shielding retinal pigment epithelium cells from high glucose-induced oxidative stress: the protective effect of phospholipase D (PLD) pathway inhibition 保护视网膜色素上皮细胞免受高糖诱导的氧化应激：磷脂酶D （PLD）途径抑制的保护作用。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2026-01-28 DOI: 10.1016/j.bbamcr.2026.120121

María S. Echevarría , Paula E. Tenconi , Vicente Bermúdez , Jorgelina M. Calandria , Nicolas G. Bazan , Melina V. Mateos

{"title":"Shielding retinal pigment epithelium cells from high glucose-induced oxidative stress: the protective effect of phospholipase D (PLD) pathway inhibition","authors":"María S. Echevarría , Paula E. Tenconi , Vicente Bermúdez , Jorgelina M. Calandria , Nicolas G. Bazan , Melina V. Mateos","doi":"10.1016/j.bbamcr.2026.120121","DOIUrl":"10.1016/j.bbamcr.2026.120121","url":null,"abstract":"<div><div>The retinal pigment epithelium (RPE) performs key roles in preserving retinal integrity and must continuously manage oxidative stress (OS). We previously demonstrated that the canonical phospholipase D isoforms, PLD1 and PLD2, mediate the RPE inflammatory response triggered by inflammatory injury. This study explores the mechanisms of modulation of OS mediated by PLD inhibition in RPE cells exposed to high glucose (HG) levels.</div><div>ARPE-19, D407 and the novel human RPE cell line ABC were cultured under HG (33 mM) or normal glucose (NG, 5.5 mM) conditions. To inhibit PLD1, PLD2, and NADPH oxidase (NOX), VU0359595 (PLD1i), VU0285655-1 (PLD2i), and diphenyleneiodonium chloride (DPI) were used, respectively. HG exposure significantly increased reactive oxygen species (ROS) levels and reduced mitochondrial membrane potential (MMP) in ARPE-19 and D407 cells. These effects were prevented by PLD1i and PLD2i in an Nrf-2 and cyclooxygenase-2 -independent manner. In ARPE-19 cells, DPI prevented OS induced by HG as well as the stress triggered by the combination of phosphatidic acid + diacylglycerol, bioactive lipids generated through the PLD pathway-. Similarly, HG elevated ROS levels in ABC cells, and this increase was prevented by PLD1i and DPI. RNAseq analysis showed differential expression of NOX family members (NOX1,2 and 4 and DUOX1 and 2) in ARPE-19 and ABC cells.</div><div>Our results demonstrate that PLDs inhibition prevent HG-induced OS in RPE cells, possibly by reducing NOX activity. The PLD pathway constitutes a novel pharmacological target to simultaneously mitigate OS and the inflammatory response, two hallmarks of retinal degenerative diseases.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120121"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146091787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of cytokines in cytokine release syndrome (CRS) after CAR T cell therapy 细胞因子在CAR - T细胞治疗后细胞因子释放综合征（CRS）中的作用。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2026-01-23 DOI: 10.1016/j.bbamcr.2026.120115

Kathrin Gabriel , Lucie Heinzerling , Louisa von Baumgarten , Marion Subklewe , Sebastian Kobold

{"title":"The role of cytokines in cytokine release syndrome (CRS) after CAR T cell therapy","authors":"Kathrin Gabriel , Lucie Heinzerling , Louisa von Baumgarten , Marion Subklewe , Sebastian Kobold","doi":"10.1016/j.bbamcr.2026.120115","DOIUrl":"10.1016/j.bbamcr.2026.120115","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR) T cell therapy has transformed the treatment landscape for hematological malignancies. However, cytokine release syndrome (CRS) remains a common and potentially severe toxicity, significantly affecting patient safety and requiring intensive clinical management. This review provides a focused synthesis on the role of cytokines in CRS after CAR T cell therapy, integrating recent mechanistic insights with clinical implications. We delineate the cellular and molecular pathways involving key cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF), describing their sources, downstream signaling events, and effects on target tissues. By bridging basic cytokine biology with clinical aspects and therapeutic strategies, this review aims to provide a comprehensive framework for understanding the role of cytokines in CRS pathophysiology, ultimately supporting the development of safer and more effective CAR T cell therapies.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120115"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Destabilization of lipoma-preferred partner by TGF-β-induced O-GlcNAcylation promotes hepatocellular carcinoma metastasis TGF-β-诱导的o - glcn酰化破坏脂肪瘤首选伴侣的稳定性，促进肝癌转移。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2026-01-24 DOI: 10.1016/j.bbamcr.2026.120117

De-ao Gong , Qin Yang , Yan-lai Zhang , Lu-yi Huang , Ni Tang , Kai Wang

{"title":"Destabilization of lipoma-preferred partner by TGF-β-induced O-GlcNAcylation promotes hepatocellular carcinoma metastasis","authors":"De-ao Gong , Qin Yang , Yan-lai Zhang , Lu-yi Huang , Ni Tang , Kai Wang","doi":"10.1016/j.bbamcr.2026.120117","DOIUrl":"10.1016/j.bbamcr.2026.120117","url":null,"abstract":"<div><div>Metastatic dissemination drives the lethal progression of hepatocellular carcinoma (HCC). A comprehensive elucidation of the post-translational modifications involved in this process is anticipated to facilitate the development of more effective strategies for inhibiting tumor cell dissemination. Here, we identified the lipoma-preferred partner (LPP) as an unexpected metastasis suppressor that is specifically downregulated in HCC. Mechanistically, transforming growth factor-β1 (TGF-β1) stabilizes glutamine-fructose-6-phosphate aminotransferase 1 (GFAT1), the rate-limiting enzyme of the hexosamine biosynthetic pathway, thereby elevating global <em>O</em>-GlcNAcylation levels. <em>O</em>-GlcNAc transferase (OGT) subsequently modifies LPP protein at serine 33 and 35, priming its ubiquitination-dependent proteasomal degradation. This degradation, mediated by the ubiquitin-protein ligase E3A (UBE3A), occurs at lysine 108 (K108) of LPP, which facilitates HCC cell migration and invasion both in vitro and in vivo. Mutagenesis of these glycosylation sites markedly attenuates HCC cell motility, invasion, and pulmonary colonization in tail-vein models. Conversely, LPP depletion accelerates metastatic outgrowth and associates with reduced patient survival. Collectively, our findings reveal a TGF-β/GFAT1/LPP axis that couples metabolic reprogramming to metastatic competence, and highlight <em>O</em>-GlcNAcylation blockade or targeted stabilization of LPP as potential therapeutic strategies against metastatic HCC.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120117"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146050189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential inclusion formation of an aggregation-prone protein reveals differences in the proteostasis capacity of neuronal cell lines 一种聚集倾向蛋白的不同包涵形成揭示了神经细胞系中蛋白质平衡能力的差异。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2026-02-17 DOI: 10.1016/j.bbamcr.2026.120124

Shannon McMahon , Dezerae Cox , Flora Cheng , Albert Lee , Justin.J. Yerbury , Heath Ecroyd

{"title":"Differential inclusion formation of an aggregation-prone protein reveals differences in the proteostasis capacity of neuronal cell lines","authors":"Shannon McMahon , Dezerae Cox , Flora Cheng , Albert Lee , Justin.J. Yerbury , Heath Ecroyd","doi":"10.1016/j.bbamcr.2026.120124","DOIUrl":"10.1016/j.bbamcr.2026.120124","url":null,"abstract":"<div><div>Maintaining proteome integrity is essential for cellular function and survival. Disruptions in proteostasis lead to the aggregation of proteins into inclusions, a process that underlies many neurodegenerative diseases. To quantitatively assess the proteostasis capacity of neuronal cells, we employed an aggregation-prone double mutant form of firefly luciferase (denoted Fluc<sup>DM</sup>) as a reporter protein. We compared two commonly used neuronal cell lines, mouse neuroblastoma cells (Neuro-2a) and a motor neuron-like hybrid line (NSC-34), to evaluate their ability to prevent the aggregation of proteins into intracellular inclusions. We observed a significantly greater propensity of Fluc<sup>DM</sup> to form inclusions in NSC-34 cells compared to Neuro-2a cells. This suggests a reduced capacity of NSC-34 cells for managing aggregation-prone proteins. Proteomic profiling of Fluc<sup>DM</sup> inclusions purified from both cell types revealed cell-type-specific engagement of the proteostasis machinery with aggregation-prone proteins. Comparing the proteomic profiles of key arms of the proteostasis network between these two cell lines revealed that the endoplasmic reticulum (ER) unfolded protein response is differentially expressed. This study establishes a quantitative platform for assessing cellular proteostasis capacity and underscores the importance of cell-type context in proteome maintenance. These insights have implications for understanding the selective vulnerability of neurons in protein misfolding disorders.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120124"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146225336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ADAM10 and ADAM17 differently mediate induced pulmonary ACE release by either direct proteolysis or indirect upregulation protein synthesis ADAM10和ADAM17通过直接蛋白水解或间接上调蛋白合成介导不同程度的肺ACE释放。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2026-01-12 DOI: 10.1016/j.bbamcr.2026.120112

Yan Yu , Aaron Babendreyer , Alessa Pabst , Anna Michely , Marie Tauscher , Christian Martin , Mark P. Kühnel , Danny D. Jonigk , Stefan Düsterhöft , Andreas Ludwig

{"title":"ADAM10 and ADAM17 differently mediate induced pulmonary ACE release by either direct proteolysis or indirect upregulation protein synthesis","authors":"Yan Yu , Aaron Babendreyer , Alessa Pabst , Anna Michely , Marie Tauscher , Christian Martin , Mark P. Kühnel , Danny D. Jonigk , Stefan Düsterhöft , Andreas Ludwig","doi":"10.1016/j.bbamcr.2026.120112","DOIUrl":"10.1016/j.bbamcr.2026.120112","url":null,"abstract":"<div><div>Angiotensin-converting enzyme (ACE) is expressed on lung endothelium and can promote hypertension and cardiovascular diseases. By the activity of the metalloproteinase ADAM10 ACE can be constitutively released from the cell membrane as soluble protease. The aim of this study was to further investigate the mechanisms underlying the enhanced production of soluble ACE under pathological conditions. Using in vitro models of primary human pulmonary microvascular endothelial cells (HPMECs) and primary human umbilical vein endothelial cells (HUVECs), as well as ex vivo models of human and murine precision-cut lung slices (PCLS), we examined ACE release in response to inflammatory stimuli, hypoxia, and protein kinase C (PKC) activation, in the presence or absence of ADAM10 and ADAM17 inhibitors. Our findings demonstrate that ADAM10 is the primary sheddase responsible for inducible ACE release, while ADAM17 contributes to ACE shedding via paracrine transcriptional induction through soluble mediators. Moreover, ACE release was differentially induced by lipopolysaccharide (LPS) and hypoxia in a manner dependent on the cellular or tissue context and exhibited species-specific differences in response to the tested stimuli. Importantly, inducibly released ACE displays enhanced catalytic activity attributable to its increased extracellular concentration. Collectively, our data reveal, for the first time, that inducible ACE release is directly mediated by ADAM10, indirectly facilitated by ADAM17, and is influenced by tissue-, context-, and species-dependent factors. This complex regulation of soluble ACE release in pathological settings may be involved in fine tuning vascular pathologies.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120112"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sox9-dependent acquisition of a drug resistant “memory state” induces reciprocal expression of Sox6 and Sox7 in BRAF melanoma 在BRAF黑色素瘤中，sox9依赖性耐药“记忆状态”的获得诱导了Sox6和Sox7的相互表达。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2026-01-22 DOI: 10.1016/j.bbamcr.2026.120118

John Abou-Hamad , Samuel Delisle , Brennan Garland , Mohammed Hersi , David Cook , Luc A. Sabourin

{"title":"Sox9-dependent acquisition of a drug resistant “memory state” induces reciprocal expression of Sox6 and Sox7 in BRAF melanoma","authors":"John Abou-Hamad , Samuel Delisle , Brennan Garland , Mohammed Hersi , David Cook , Luc A. Sabourin","doi":"10.1016/j.bbamcr.2026.120118","DOIUrl":"10.1016/j.bbamcr.2026.120118","url":null,"abstract":"<div><div>In melanoma, SOX9 and SOX10 are markers of the mesenchymal and melanocytic state, respectively. Using a panel of BRAF<sup>V600E</sup> positive YUMM lines, we find that, following chronic vemurafenib treatment, SOX10 is lost whereas SOX9 is induced. Overexpression or knock-down of either SOX9 or SOX10 had no impact on vemurafenib sensitivity. However, we find that SOX9 is necessary to program a vemurafenib-resistance memory state following a drug holiday in vitro. RNA-Seq studies show that the loss of <em>Sox10</em> represents an intermediate state that is accompanied by the loss of <em>Sox6</em> and the induction of <em>Sox7, Sox9</em> and other phenotype switching markers. However, SOX7 expression is not sufficient to induce vemurafenib resistance. Upon acquired drug resistance, we observed differential chromatin accessibility in the <em>Sox9</em> and <em>Sox10</em> upstream regions, supporting their activation and repression, respectively. Overall, our data show that the loss of SOX10 and SOX9 induction are critical to program drug resistance. Furthermore, we show that the YUMM cell lines represent a good murine model to investigate transitions to an acquired drug resistant state.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120118"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Matrix stiffness-induced NARF promotes hepatocellular carcinoma progression by enhancing LEF1-mediated transcription 基质刚度诱导的NARF通过增强lef1介导的转录促进肝细胞癌的进展。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2026-02-06 DOI: 10.1016/j.bbamcr.2026.120122

Xuelian Xiao, Kangsheng Tu

{"title":"Matrix stiffness-induced NARF promotes hepatocellular carcinoma progression by enhancing LEF1-mediated transcription","authors":"Xuelian Xiao, Kangsheng Tu","doi":"10.1016/j.bbamcr.2026.120122","DOIUrl":"10.1016/j.bbamcr.2026.120122","url":null,"abstract":"<div><div>Liver fibrosis and cirrhosis generate a stiff extracellular matrix (ECM) niche that is closely associated with hepatocellular carcinoma (HCC) initiation and progression. Although multiple pathways and molecules are implicated in ECM rigidity-induced mechanical force transduction, the precise mechanism by which ECM rigidity drives HCC progression remain to be fully elucidated. In this study, we identified nuclear prelamin A recognition factor (NARF) as a novel matrix stiffness-responsive gene, whose transcription is directly regulated by the mechanosensor Yes-associated protein (YAP). Clinically, NARF exhibited high expressions in HCC tissues, and its overexpression was closely correlated with poor prognostic outcomes in HCC patients. Functionally, NARF knockdown significantly inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of HCC cells in vitro, whereas NARF overexpression enhanced these cellular processes. NARF silencing attenuated HCC cell growth and lung metastasis in vivo. RNA-sequencing analysis revealed a strong correlation of NARF with Wnt signaling activation. Further experiments confirmed that NARF positively regulated the expression of key Wnt target genes (MYC, CCND1, SNAIL, and TWIST1) in HCC cells. Mechanistically, NARF recruited acetyltransferase EP300 to enhance H3K27 acetylation at lymphoid enhancer binding factor 1 (LEF1)-binding sites, thereby amplifying LEF1-dependent transcriptional activity. LEF1 knockdown markedly abrogated NARF-mediated oncogenic activity in vitro and in vivo, confirming LEF1 as a critical downstream effector of NARF. Collectively, our findings identify NARF as stiffness-responsive driver that is transcriptionally regulated by YAP protein in HCC. By activating LEF1-mediated Wnt signaling in an EP300 dependent manner, NARF promotes HCC growth and metastasis, highlighting its potential as a prognostic biomarker and therapeutic target for HCC.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120122"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neutrophil-mediated modulation of tumor angiogenesis: From proangiogenic mediators to extracellular vesicles 中性粒细胞介导的肿瘤血管生成调节：从促血管生成介质到细胞外囊泡。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2026-02-23 DOI: 10.1016/j.bbamcr.2026.120126

Weronika Jurczyk , Jadwiga Jablonska , Mateusz Smolarz

{"title":"Neutrophil-mediated modulation of tumor angiogenesis: From proangiogenic mediators to extracellular vesicles","authors":"Weronika Jurczyk , Jadwiga Jablonska , Mateusz Smolarz","doi":"10.1016/j.bbamcr.2026.120126","DOIUrl":"10.1016/j.bbamcr.2026.120126","url":null,"abstract":"<div><div>Angiogenesis is a tightly controlled physiological process that enables the formation of new blood vessels. Under normal conditions, it is regulated by a balance between pro- and anti-angiogenic signals. In cancer, this equilibrium is disrupted, and angiogenesis becomes a pathological mechanism that supports tumor growth, progression, and metastasis. The process is orchestrated by a variety of cells, including endothelial cells (EC), fibroblasts, macrophages, platelets, neutrophils, and cancer cells, which release chemical mediators. Among them, growth factors such as VEGF, FGF, PDGF, angiopoietins, and TGF-β play a central role by activating signaling pathways that stimulate endothelial proliferation, migration, survival, and extracellular matrix (ECM) remodeling. Their activity drives the “angiogenic switch,” a hallmark of early tumor development. Neutrophils, the most abundant immune cells in circulation, exert a dual influence on this process. Pro-tumor neutrophils enhance angiogenesis through the secretion of VEGF-A, TGF-β, MMP-9, IL-8, and the release of neutrophil extracellular traps, facilitating vascular permeability and tumor progression. Conversely, anti-tumor neutrophils release TNF-α, IL-12, and chemokines such as CXCL9/10, which inhibit angiogenesis and restrain tumor expansion. Recently, small extracellular vesicles (sEVs) have emerged as critical mediators of intercellular communication. Neutrophil-derived sEVs transport proangiogenic miRNAs, proteins, and signaling molecules that influence endothelial activation, epithelial-to-mesenchymal transition, therapy resistance, and metastatic potential. Given their unique molecular cargo, they represent potential modulators of tumor angiogenesis, although studies in this area remain limited. This review summarizes the principal mechanisms of angiogenesis, the multifaceted role of neutrophils in shaping tumor vasculature, and the emerging contribution of neutrophil-derived sEVs.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120126"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147301605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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