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

Insights into the regulation and signaling landscape of cardiotrophin-like cytokine factor 1 (CLCF1) 心肌营养因子样细胞因子1 （CLCF1）的调控和信号转导研究。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2026-02-07 DOI: 10.1016/j.bbamcr.2026.120123

Marine Rousseau , France Côté , Sylvain Chemtob , Jean-François Gauchat , Sarah Pasquin , Sylvie Lesage

{"title":"Insights into the regulation and signaling landscape of cardiotrophin-like cytokine factor 1 (CLCF1)","authors":"Marine Rousseau , France Côté , Sylvain Chemtob , Jean-François Gauchat , Sarah Pasquin , Sylvie Lesage","doi":"10.1016/j.bbamcr.2026.120123","DOIUrl":"10.1016/j.bbamcr.2026.120123","url":null,"abstract":"<div><div>Cardiotrophin-like cytokine factor 1 (CLCF1) is an essential gene that shows exceptional sequence conservation among vertebrates. <em>CLCF1</em> loss-of-function mutations cause Crisponi/cold-induced sweating syndrome-2, a disorder with severe and complex phenotypes, underscoring the non-redundant roles of CLCF1. Initially identified as a member of the interleukin-6 (IL-6) cytokine family with activity in neurons and immune cells, CLCF1 is now recognized for broader roles in thermoregulation, glomerular function, myelopoiesis, oncogenesis, and muscle fitness. Despite growing interest in the multifaceted biology of CLCF1, the mechanisms regulating its transcription, translation, secretion, receptor binding, and signaling remain incompletely understood. This review integrates data from multiple open databases and functional studies to outline the current state of knowledge regarding CLCF1 regulatory landscape, receptor interactions, and downstream signaling. It also highlights recent discoveries about the CLCF1 interactome and intracellular functions and underlines its emerging potential as a therapeutic target.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120123"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146148935","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

Mutant-specific dysfunction of RHOBTB2 impairs mitochondrial function and Na+/K+-ATPase levels in a cell model 在细胞模型中，RHOBTB2突变特异性功能障碍损害线粒体功能和Na+/K+- atp酶水平

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2025-12-31 DOI: 10.1016/j.bbamcr.2025.120103

Sachiko Miyamoto , Shun-ichi Yamashita , Hazrat Belal , Mitsuhiro Kato , Tomotake Kanki , Hirotomo Saitsu

{"title":"Mutant-specific dysfunction of RHOBTB2 impairs mitochondrial function and Na+/K+-ATPase levels in a cell model","authors":"Sachiko Miyamoto , Shun-ichi Yamashita , Hazrat Belal , Mitsuhiro Kato , Tomotake Kanki , Hirotomo Saitsu","doi":"10.1016/j.bbamcr.2025.120103","DOIUrl":"10.1016/j.bbamcr.2025.120103","url":null,"abstract":"<div><div><em>RHOBTB2</em> is an atypical Rho GTPase implicated in developmental and epileptic encephalopathy, yet its pathogenic mechanisms remain poorly understood. In this study, we established a cell model in which <em>RHOBTB2</em> expression was induced by a doxycycline-inducible system to investigate the functional consequences of disease-associated <em>RHOBTB2</em> mutants. Protein expression and localization analyses revealed mutant-specific behaviors: GTPase-domain mutants such as D92H and W217C showed no significant difference in RHOBTB2 protein levels compared with WT, while hotspot mutants (R461H, R485C, R489Q) exhibited increased RHOBTB2 protein levels with nuclear and mitochondrial accumulation. RNA-seq analysis revealed that cells expressing each mutant showed distinct transcriptomic changes. Notably, induction of the R489Q mutant caused a robust downregulation of ion channel-related genes, supporting its potential role in disrupting neuronal excitability. Furthermore, expression of mutant RHOBTB2 led to a reduction in Na<sup>+</sup>/K<sup>+</sup>-ATPase protein levels via a lysosome-dependent degradation pathway. This effect was particularly prominent in GTPase-domain mutants (D92H and W217C), suggesting a mechanistic link between mutant RHOBTB2 and impaired ion homeostasis. Moreover, the R489Q and W217C mutants impaired mitochondrial respiration, whereas other mutants did not show detectable mitochondrial dysfunction. Importantly, the Y284D cancer-associated mutant did not share these phenotypes, highlighting the diversity of functional outcomes across different mutation sites. The observed dysregulation of ion transport pathways and mitochondrial impairment in some mutants may represent key mechanisms underlying seizure susceptibility and other neurological manifestations in <em>RHOBTB2</em>-associated encephalopathies.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120103"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883665","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

Friend or foe: New cytokine players in beta cell failure in type 1 diabetes mellitus 是敌是友：1型糖尿病β细胞衰竭的新细胞因子。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2026-01-19 DOI: 10.1016/j.bbamcr.2026.120113

Ewa Gurgul-Convey, Ortwin Naujok

引用次数: 0

The language of cytokines: Decoding immune signals with information theory 细胞因子的语言：用信息论解码免疫信号。

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.2026.120119

Sophie Streuber , Emelie Rieneck , Fred Schaper , Anna Dittrich

{"title":"The language of cytokines: Decoding immune signals with information theory","authors":"Sophie Streuber , Emelie Rieneck , Fred Schaper , Anna Dittrich","doi":"10.1016/j.bbamcr.2026.120119","DOIUrl":"10.1016/j.bbamcr.2026.120119","url":null,"abstract":"<div><div>Communication between cells is fundamental for maintaining and restoring homeostasis in multicellular organisms under both physiological and pathological conditions. A variety of mechanisms for encoding, transmitting, and decoding information have evolved. Information theory, originally developed in engineering, has been increasingly applied to dissect how cells process and exchange signals. Yet, biological systems exhibit distinctive properties that pose conceptual and quantitative challenges not encountered in technical systems. In this review, we examine how cellular networks manage and often exploit the intrinsic heterogeneity of cell populations. We discuss how individual cells and cell populations sense cytokine stimulus strength and specificity, and how regulatory proteins shape not only signalling dynamics but also the capacity and robustness of information transmission. From an information theoretical perspective, health can be viewed as a state of efficient and reliable cellular communication, whereas disease reflects the loss or distortion of robust cellular communication. We conclude that information theory offers an intuitive framework for biologists seeking to unravel the principles of cytokine signalling.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120119"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043576","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

Development of a TEAD-independent reporter system for specific and sensitive measurement of YAP/TAZ activity 开发一个独立于tead的报告系统，用于特异性和敏感性测量YAP/TAZ活性

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.2026.120111

Jiuge Zhang , Wenqian Yang , Qiuyun Yuan , Fei Huang , Die Lv , Yixin Zhang , Xiaoqiang Xia , Yuan Yue , Xiaodong Feng

{"title":"Development of a TEAD-independent reporter system for specific and sensitive measurement of YAP/TAZ activity","authors":"Jiuge Zhang , Wenqian Yang , Qiuyun Yuan , Fei Huang , Die Lv , Yixin Zhang , Xiaoqiang Xia , Yuan Yue , Xiaodong Feng","doi":"10.1016/j.bbamcr.2026.120111","DOIUrl":"10.1016/j.bbamcr.2026.120111","url":null,"abstract":"<div><div>Accurate quantification of Yes-associated protein (YAP) and its paralog TAZ is critical for understanding their biological functions, however, existing reporter systems are constrained by their reliance on endogenous TEAD transcription factors. Here, we developed an endogenous TEAD-independent reporter system for YAP/TAZ activity, based on the GAL4-UAS system. The construct consists of the GAL4 DNA-binding domain (DBD) fused to the YAP-binding domain (YBD) of TEAD4, with the native TEAD DNA-binding domain (TEA) removed. Structural modeling of the G-TEAD4(217) fusion protein confirmed high similarity to experimentally resolved TEAD4-YAP or GAL4-DNA bound structures and revealed surface properties consistent with functional domain separation. Functional assays showed that the reporter reliably responded to both YAP knockdown and overexpression. Compared to the conventional 8 × GTIIC reporter, G-TEAD4(217) exhibited higher sensitivity and remained unaffected by TEAD4 silencing, confirming reporter specificity and TEAD independence. In addition, the system demonstrated its suitability for compound screening by validating known YAP inhibitors across a number of high-YAP cancer cell lines. A single-plasmid lentiviral version LV-G-TEAD4(217) was also developed to enable stable transduction and potential in vivo use. Together, these findings demonstrate that G-TEAD4(217) represents a sensitive, specific, and modular reporter platform for analyzing YAP/TAZ transcriptional activity in diverse biological settings.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120111"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974086","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

Regulation of E-cadherin by mixed lineage kinase 3 (MLK3) mediates cell adhesion in ovarian cancer spheroids 混合谱系激酶3 （MLK3）调控e -钙粘蛋白介导卵巢癌球体细胞粘附

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.2026.120106

Mariah C.J. Rozier, Danielle N. Adjei, Rachel A. Radtke, Deborah N. Chadee

{"title":"Regulation of E-cadherin by mixed lineage kinase 3 (MLK3) mediates cell adhesion in ovarian cancer spheroids","authors":"Mariah C.J. Rozier, Danielle N. Adjei, Rachel A. Radtke, Deborah N. Chadee","doi":"10.1016/j.bbamcr.2026.120106","DOIUrl":"10.1016/j.bbamcr.2026.120106","url":null,"abstract":"<div><div>Mixed lineage kinase 3 (MLK3) is a serine/threonine mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K) that activates MAPK signaling pathways and promotes cell proliferation, migration and invasion. E-cadherin is an essential cell adhesion protein that mediates cell-cell interactions in epithelial adherens junctions and is crucial for the integrity of tissues and organs. Here, we demonstrate that MLK3 siRNA knockdown or kinase inhibition significantly impaired spheroid formation in SKOV3, TOV112D and OVCAR3 ovarian cancer cells, that was rescued by overexpression of E-cadherin. Endogenous MLK3 and E-cadherin were co-immunoprecipitated from ovarian cancer cell lysates; and recombinant MLK3 and E-cadherin directly interacted <em>in vitro</em>. MLK3 phosphorylates E-cadherin and has a positive regulatory effect on E-cadherin protein stability. Like E-cadherin, MLK3 is localized to the plasma membrane at regions of cell-cell contact, and MLK3 also has cytoplasmic and nuclear localization. Neither the MLK3-E-cadherin interaction nor the plasma membrane localization of MLK3 is dependent on β-catenin. Collectively, these results indicate a novel function for MLK3 in regulating E-cadherin protein stability, cell adhesion, and ovarian cancer spheroid formation.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120106"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145923181","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

The dual face of reprogrammed proteostasis in cancer and its epigenetic regulation: A survival option and a therapeutic opportunity 癌症中重编程蛋白停滞及其表观遗传调控的双重面孔：生存选择和治疗机会。

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.2026.120116

Mara Cirone

{"title":"The dual face of reprogrammed proteostasis in cancer and its epigenetic regulation: A survival option and a therapeutic opportunity","authors":"Mara Cirone","doi":"10.1016/j.bbamcr.2026.120116","DOIUrl":"10.1016/j.bbamcr.2026.120116","url":null,"abstract":"<div><div>Proteostasis is essential for cellular homeostasis and is maintained through an integrated network encompassing the unfolded protein response (UPR), molecular chaperones such as heat shock proteins (HSPs), and degradative systems including the ubiquitin–proteasome and autophagy-lysosomal pathways. In cancer, microenvironmental stresses such as hypoxia, nutrient deprivation, and oxidative imbalance impose a persistent proteotoxic burden, driving a context-dependent rewiring of these pathways that supports tumor survival, plasticity, and progression. Increasing evidence indicates that the functional outcomes of proteostasis responses, whether adaptive or cytotoxic, are determined by specific molecular cues, including the intensity and duration of stress, pathway crosstalk, and cell-intrinsic oncogenic alterations. Epigenetic mechanisms, comprising DNA methylation, histone modifications, and non-coding RNAs, further fine-tune these proteostatic programs by modulating the expression and activity of key regulators, thereby contributing to drug resistance but also generating cancer-selective vulnerabilities. This review provides a structured and mechanistic overview of how UPR, chaperone networks, and protein degradation pathways are remodeled in cancer and examines the epigenetic determinants that shape their adaptive behavior. Finally, we discuss emerging translational opportunities arising from the dual role of proteostasis in cancer, highlighting therapeutic strategies that exploit the dynamic interplay between proteostatic and epigenetic regulation.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120116"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046059","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 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

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