Tissue & cell最新文献

{"title":"Liposome-engineered therapeutics: A promising frontier in ovarian cancer treatment","authors":"Helia Mavaddat ,&nbsp;Amirreza Peyrovinasab ,&nbsp;Shirin Sirous Kabiri ,&nbsp;Nasim Basiri ,&nbsp;Ilia Khayatan ,&nbsp;Seyed Mehrad Razavi ,&nbsp;Malak Hekmati ,&nbsp;Atena Esmaeili ,&nbsp;Tannaz Jamialahmadi ,&nbsp;Amir Hossein Abdolghaffari ,&nbsp;Prashant Kesharwani ,&nbsp;Amirhossein Sahebkar","doi":"10.1016/j.tice.2025.103138","DOIUrl":"10.1016/j.tice.2025.103138","url":null,"abstract":"<div><div>Ovarian cancer remains a leading cause of gynecological cancer-related mortality, with epithelial ovarian carcinoma, germ cell tumors, and stromal tumors being the most prevalent types. The disease is classified based on the Fédération Internationale de Gynécologie et d′Obstétrique (FIGO) staging system, and its incidence increases with age. Standard treatment strategies, including taxanes, platinum-based drugs, monoclonal antibodies, and poly (ADP-ribose) polymerase (PARP) inhibitors, as well as emerging gene and immunotherapies, often suffer from significant adverse effects and limited efficacy. To overcome these challenges, advanced drug delivery systems are essential for enhancing therapeutic outcomes while minimizing toxicity. Liposomes have emerged as a promising nanocarrier for targeted drug delivery in ovarian cancer therapy, offering improved drug stability, prolonged circulation time, and enhanced tumor-specific accumulation. Functional modifications, such as ligand conjugation and combination therapies, further optimize their therapeutic potential. This review discusses recent advancements in liposome-based drug delivery for ovarian cancer, highlighting their benefits, challenges, and future directions in improving treatment efficacy.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103138"},"PeriodicalIF":2.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Betaine promotes the osteogenic differentiation of SCAPs via inhibiting NUMB","authors":"Meiyue Wang ,&nbsp;Jiaman Zhu ,&nbsp;Xiaoyu Zheng ,&nbsp;Zejie Wu ,&nbsp;Runtao Gao","doi":"10.1016/j.tice.2025.103142","DOIUrl":"10.1016/j.tice.2025.103142","url":null,"abstract":"<div><div>Betaine, a known modulator of mesenchymal stem cells (MSCs) differentiation, has demonstrated potential in enhancing osteogenesis. However, its specific role in the osteogenic differentiation of stem cells from the apical papilla (SCAPs) has not been fully elucidated. In this study, we found that betaine (10 mM) significantly enhanced the osteogenesis of SCAPs, as evidenced by increased ALP activity and mineralized nodule formation (<em>p</em> &lt; 0.05). Betaine downregulated NUMB expression, a negative regulator of osteogenic differentiation, during the induction process. Overexpression of NUMB counteracted the promotive effects of betaine on SCAPs osteogenesis and NUMB knockdown enhances betaine effects. These findings suggest that betaine regulates the osteogenic differentiation of SCAPs via inhibition of NUMB and may serve as a novel therapeutic approach for maxillofacial bone repair, with NUMB as a potential drug target.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103142"},"PeriodicalIF":2.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The early recovery phase from spontaneous testicular degeneration in the blue shark, Prionace glauca: Large oblong interstitial cells and the clearance of redundant spermatid-associated Sertoli cells","authors":"Leon Mendel McClusky","doi":"10.1016/j.tice.2025.103139","DOIUrl":"10.1016/j.tice.2025.103139","url":null,"abstract":"<div><div>The blue shark (<em>Prionace glauca</em>) maintains voluminous seminal vesicles year-round. And yet, the diametrically arranged testis’s successive rows of spherical germ/ Sertoli cell units (spermatocysts) reveal a gradient of cyst stage-specific, Sertoli cell-only phagocytic clearing activities some time after the spontaneous appearance of protracted, massive multinucleate spermatogonial death seen in summer-mating individuals. Herewith novel findings concerning a hitherto unknown though distinctive interstitial cell type, here termed an oblong reticular-patterned (ORP) cell, observed in both western North Atlantic and Mediterranean Sea blue sharks and that showed cyst-encircling behaviors around far-progressed, phagocytically cleared, earlier spermiogenesis-arrested cysts. The proportion of ORP-positive cysts that were engaged in, or showed completed Sertoli phagocytic clearing of spermatids was significantly (P &lt; 0.01) 3-fold greater in the early recovery phase condition than in the testis condition showing massive multinucleate death. The Sertoli nuclei were the last contents to disappear in the ORP-encased cyst. Bar the odd ORP cell-aggregation at the mature pole, the fully recovered testis sampled in late August lacked all the above. Perusal of a single testicular cross-section showing the diametrically radiating, successive rows of cyst stages facilitates the simultaneous scrutiny of cellular rearrangements in prespermatogenesis at the testis’s immature pole and that of the conclusion of spermatogenesis at the mature pole. Scrutiny of the dynamic stromal environment where cysts are formed at the immature pole revealed the distinctive and insidious ORPs among not-yet sequestered primary spermatogonia, which allude to their alternative fate as future Sertoli cells proper.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103139"},"PeriodicalIF":2.5,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of decellularization processes on the immune response and compatibility of tissues","authors":"Azadeh Nochalabadi ,&nbsp;Mozafar Khazaei ,&nbsp;Sepehr Zamani ,&nbsp;Leila Rezakhani","doi":"10.1016/j.tice.2025.103135","DOIUrl":"10.1016/j.tice.2025.103135","url":null,"abstract":"<div><div>Extracellular matrix (ECM)-based biologic scaffolds are widely employed in therapeutic tissue regeneration applications. The immunologic rejection and donor shortage caused by cellular components in traditional tissue/organ transplantation may be greatly alleviated by these decellularized scaffolds. Decellularization, a crucial step in the production of ECM scaffolds, removes immunogen-containing cell components and significantly reduces the immunogenicity while improving the biocompatibility of the final scaffolds. However, the application of these bio-scaffolds still confronts the major immunologic challenges. Understanding how a scaffold interacts with the host immune system is essential for choosing an appropriate one. Various techniques have been developed for this purpose. The ECM is damaged by all decellularization techniques, including both chemical and physical methods. Nevertheless, the consequences of various techniques vary, making some of these operations better than alternative techniques for preserving ECM structure. The host's immune system reacts in a complicated way to a decellularized scaffold. Numerous immune cells may have an impact on this process, but the properties, preparation, and alteration of the decellularized scaffold can also have a big impact on this response. These elements may operate alone or in combination to cause immune cells to polarize in either a pro-inflammatory or pro-healing manner. In this study, we have thoroughly examined the variables that could affect the immune system's reaction to a decellularized scaffold in this study.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103135"},"PeriodicalIF":2.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyaluronic acid-based three dimensional scaffold in combination with hyperbaric oxygen therapy promote diabetic wound healing","authors":"Mohammed Alissa,&nbsp;Suad A. Alghamdi,&nbsp;Abdulkarim S. Binshaya","doi":"10.1016/j.tice.2025.103136","DOIUrl":"10.1016/j.tice.2025.103136","url":null,"abstract":"<div><div>Diabetic wounds represent a major clinical challenge due to impaired healing processes such as reduced angiogenesis, chronic inflammation, and defective collagen remodeling. This study aimed to evaluate the therapeutic potential of a hyaluronic acid-based three-dimensional scaffold (HAS) in combination with hyperbaric oxygen therapy (HBOT) in promoting wound healing in a diabetic rat model. Diabetes was induced in Wistar rats, and full-thickness excisional wounds were created. Diabetic animals were divided into control, HBOT, HAS, and HAS+HBOT groups. Additionally, non-diabetic untreated rats (Healthy group) were considered as a control. Wound healing progression was assessed via wound contraction rate, stereological evaluations (fibroblast counts, neutrophil infiltration, and blood vessel density), cytokine profiling (VEGF, TGF-β, TNF-α, IL-1β), collagen deposition (Masson's trichrome, hydroxyproline assay), and biomechanical properties (maximum force and energy absorption). Wound contraction was significantly accelerated in all treatment groups compared to controls, with the HAS+HBOT group showing the greatest improvement (p &lt; 0.05). Histological analysis revealed enhanced fibroblast proliferation and neovascularization, along with reduced neutrophil infiltration in treated groups, particularly in the HAS+HBOT group. Collagen content was markedly higher in treated wounds, supported by increased hydroxyproline levels and trichrome staining. The HAS+HBOT group also demonstrated elevated VEGF and TGF-β levels and decreased expression of TNF-α and IL-1β, indicating a favorable balance between regeneration and inflammation. Biomechanical testing confirmed superior maximum force and energy absorption in the HAS+HBOT group compared to all others. The combination of HAS and HBOT significantly enhances diabetic wound healing by promoting tissue regeneration, modulating inflammation, and restoring biomechanical integrity. This strategy holds promise as an effective therapeutic approach for chronic diabetic wounds.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103136"},"PeriodicalIF":2.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the effects of resveratrol, lutein, and crocetin on ARPE-19 cells induced with oxidative damage by H2O2","authors":"Ayşegül Yabaş ,&nbsp;Veysel Levent Karabaş ,&nbsp;Selenay Furat ,&nbsp;Ecem Önder Tokuç ,&nbsp;Ahmet Öztürk ,&nbsp;Candan Altuntaş ,&nbsp;Özgür Doğa Özsoy ,&nbsp;Gökhan Duruksu ,&nbsp;Yusufhan Yazır","doi":"10.1016/j.tice.2025.103133","DOIUrl":"10.1016/j.tice.2025.103133","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to evaluate and compare the antioxidant effects, influence on autophagy and mitophagy, and impact on cell viability of resveratrol, lutein, and crocetin in hydrogen peroxide (H₂O₂)-induced oxidative damage in ARPE-19 cells as an in vitro model of age-related macular degeneration (AMD).</div></div><div><h3>Methods</h3><div>Oxidative damage was induced in ARPE-19 cells by exposure to 800 μM H₂O₂ for 1 h. Cell viability was assessed using the WST-1 assay. Subsequently, ARPE-19 cells were treated with lutein (5 and 10 μM), crocetin (10 and 20 μM), or resveratrol (100 μM), and the levels of oxidative damage biomarkers including malondialdehyde (MDA), glutathione (GSH), and nitric oxide (NO) were quantified via spectrophotometry. The autophagy- and mitophagy-related markers, LC3B, PINK1, and PARKIN, were visualized using confocal microscopy, and LC3B and PARKIN were further evaluated by western blotting (WB).</div></div><div><h3>Results</h3><div>Cell viability results were 100 % in the control group, decreased to 73.5 % and 69.1 % with 10 and 20 μM crocetin, 62.7 % and 59.3 % with 5 and 10 μM lutein, and 52.7 % with 100 μM resveratrol, respectively, while H₂O₂ exposure reduced viability to 0.04 %. Exposure to H₂O₂ (800 µM, 1 h) induced significant oxidative damage in ARPE-19 cells, as indicated by a reduction in GSH levels (p &lt; 0.01) and an increase in MDA (p &lt; 0.001) and NO (p &lt; 0.001) compared to the control group, along with a notable decrease in WST-1 viability. Among the interventions, 10 µM crocetin significantly decreased MDA (p = 0.019) and NO (p = 0.05) levels compared to those in the damage group, although the 20 µM concentration also reduced these markers without achieving statistical significance. 5 µM Lutein significantly reduced NO levels compared to the damage group, whereas reductions in MDA at concentrations of 5–10 µM were not statistically significant. GSH levels exhibited a numerical, albeit non-significant, increase with 10 µM lutein (p = 0.09), and showed modest, non-significant increases with crocetin and resveratrol. The highest LC3B expression was observed in the 5 μM lutein group compared to control and other treatment groups, while PARKIN expression was significantly elevated in the 10 μM lutein, 20 μM crocetin, and 100 μM resveratrol groups, with 20 μM crocetin and resveratrol levels also exceeding lutein 5 μM.</div></div><div><h3>Conclusions</h3><div>10 μM Crocetin demonstrated the strongest antioxidant protection, while 5 μM lutein primarily improved cell survival, likely through autophagy activation and 100 μM resveratrol also activated both autophagy and mitophagy. These results highlighted the complementary concentration-dependent mechanisms of natural antioxidants in protecting RPE cells from oxidative stress related to AMD.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103133"},"PeriodicalIF":2.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145027392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intracellullar cholesterol accumulation caused by HBV induces ATF6-mediated endoplasmic reticulum stress to trigger endoplasmic reticulophagy","authors":"Yongxu Lin ,&nbsp;Pingying Jiang ,&nbsp;Weiqi Cai ,&nbsp;Yongzhu Huang ,&nbsp;Qiuyan Lin ,&nbsp;Mingrong Wang ,&nbsp;Fenglin Chen ,&nbsp;Yuanlin Qi ,&nbsp;Dan Li","doi":"10.1016/j.tice.2025.103134","DOIUrl":"10.1016/j.tice.2025.103134","url":null,"abstract":"<div><h3>Backgroud</h3><div>Hepatitis B virus (HBV) infection can cause cholesterol accumulation, induce endoplasmic reticulum stress (ERS) and enhance autophagy in hepatocytes. However, the mechanisms underlying these interactions remain unclear, as well as the potential benefit of cholesterol-lowering treatment in patients with chronic hepatitis B (CHB). Therefore, the effects of of cholesterol accumulation caused by HBV on ERS and autophagy were explored in this study, aiming to identify the key molecules mediating the crosstalk between ERS and endoplasmic reticulophagy (ER-phagy).</div></div><div><h3>Methods</h3><div>Bioinformatics, immunohistochemistry (IHC), proteomics, western blot, and transmission electron microscopy (TEM) were used to analyse clinical specimens, HBV transgenic animal and cell models.</div></div><div><h3>Results</h3><div>Analysis of Gene Expression Omnibus (GEO) database demonstrated that the transcription levels of LDLR, SREBF2/SREBP2, ATF6, MAP1LC3B/LC3B and SQSTM1/P62 in CHB tissues were higher than those in normal liver tissues. The IHC results showed that the expressions of LDLR, SREBP2, GRP78, ATF6, LC3B, P62 and FAM134B in CHB tissues were higher than those in normal liver tissues. The free cholesterol content, the expression of GRP78, ATF6, LC3B II, P62 and FAM134B were higher in the livers of HBV transgenic mice and HepG2.2.15 cells compared with their control groups. TEM showed endoplasmic reticulum (ER) expansion and degranulation, as well as ER-phagy, in the livers of HBV transgenic mice and HepG2.2.15 cells. Furthermore, melatonin administration, an ATF6 inhibitor, attenuated hepatic inflammation, alleviated ERS, downregulated ATF6 expression, and inhibited ER-phagy in HBV transgenic mice and HepG2.2.15 cells. Fatostatin administration, a cholesterol synthesis inhibitor, attenuated hepatic inflammation, decreased the free cholesterol content, alleviated ERS, downregulated GRP78 and ATF6 expression, and inhibited ER-phagy in HBV transgenic mice and HepG2.2.15 cells</div></div><div><h3>Conclusion</h3><div>HBV infection leads to cholesterol accumulation in hepatocytes, which promotes ATF6-mediated ERS and FAM134B-mediated ER-phagy. Reducing intracellular cholesterol accumulation alleviates ATF6-mediated ERS, inhibits FAM134B-mediated ER-phagy, and attenuates hepatic inflammation. ATF6 may represent a promising therapeutic target for an adjuvant treatment of CHB. Our study provides experimental evidence for the use of statin as an adjuvant treatment of CHB.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103134"},"PeriodicalIF":2.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"A compound of concentrated growth factor and periodontal ligament stem cell-derived conditioned medium\" [Tissue Cell 65 (2020) 101373].","authors":"Z Aghamohamadi, M Kadkhodazadeh, M Torshabi, F Tabatabaei","doi":"10.1016/j.tice.2025.103084","DOIUrl":"https://doi.org/10.1016/j.tice.2025.103084","url":null,"abstract":"","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":" ","pages":"103084"},"PeriodicalIF":2.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin alleviates cholestatic liver injury through modulating gut microbiota and activating the NRF2/HO-1 antioxidant pathway","authors":"Shijing Dong ,&nbsp;Jiangpeng Liu ,&nbsp;Chenyang Xuan ,&nbsp;Simin Zhou ,&nbsp;Zongze Han,&nbsp;Chenhui Zhu,&nbsp;Nian Chen,&nbsp;Ruiyun Liu,&nbsp;Weirong Wang,&nbsp;Hongyu Chu,&nbsp;Xue Zhang,&nbsp;Hui Yang,&nbsp;Man Liu,&nbsp;Liping Guo,&nbsp;Lu Zhou","doi":"10.1016/j.tice.2025.103131","DOIUrl":"10.1016/j.tice.2025.103131","url":null,"abstract":"<div><div>Cholestasis is a pathological state characterized by the dysfunction of bile acid flow, which could lead to liver fibrosis, cirrhosis, and even liver failure, but its therapeutic agents are limited. The aim of this study was to investigate the therapeutic potential and underlying mechanism of melatonin on cholestatic liver injury. C57BL/6 J mice were fed with 0.05 % 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine (DDC) diet to induce cholestatic liver injury, with or without daily intraperitoneal injection of 20 mg/kg melatonin. The supplementation of melatonin alleviated cholestatic liver injury through improving liver histopathology and abnormal serum indicators reflecting liver function. Meanwhile, melatonin treatment inhibited the hepatic inflammatory infiltration and release of pro-inflammatory cytokines. Moreover, liver fibrosis caused by cholestasis was mitigated by melatonin via reducing collagen deposition and pro-fibrogenic factors. Furthermore, the gut microbiota dysbiosis and impaired intestinal barrier induced by DDC were mitigated after melatonin treatment. Notably, melatonin activated the cholangiocyte nuclear factor erythroid 2-related factor 2 (NRF2) / heme oxygenase-1 (HO-1) signalling pathway through melatonin receptor 1 A (MTNR1A) to protect the liver from oxidative stress damage. In conclusion, melatonin is a potential therapeutic agent for cholestatic liver injury, possibly acting by modulating gut microbiota and activating the NRF2/HO1 pathway.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103131"},"PeriodicalIF":2.5,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor microenvironment-driven ST6Gal-Ⅰ activation promotes aggressiveness in gastric signet-ring cell carcinoma via ITGβ1/FAK/Paxillin signaling","authors":"Shuhong Zeng ,&nbsp;Lihuiping Tao ,&nbsp;Yingjie Gao ,&nbsp;Xueying Yang ,&nbsp;Zhiyu Li ,&nbsp;Ziwen Li ,&nbsp;Luhua Wu ,&nbsp;Zhengchen Ping ,&nbsp;Qian Zhao ,&nbsp;Jiayi Gu ,&nbsp;Liu Li ,&nbsp;Dongdong Sun ,&nbsp;Weixing Shen","doi":"10.1016/j.tice.2025.103130","DOIUrl":"10.1016/j.tice.2025.103130","url":null,"abstract":"<div><h3>Background</h3><div>Poorly cohesive gastric carcinoma, particularly signet-ring cell (SRC) carcinoma, is an aggressive gastric cancer (GC) subtype with high metastatic potential and poor prognosis. Sialylation plays a critical role in tumor progression, but its functional significance in SRC malignancy and microenvironmental regulation remains unclear. This study investigated ST6Gal-Ⅰ’s mechanistic contributions to SRC aggressiveness, focusing on epithelial-mesenchymal transition (EMT), stromal interactions, and metastatic signaling.</div></div><div><h3>Methods</h3><div>Multiple SRC and non-SRC GC cell lines, patient-derived organoids, and stromal cells (MSCs, HUVECs) were utilized. Techniques included co-culture models (transwell and direct contact), immunohistochemistry, western blotting, functional assays (transwell migration, wound healing, sphere/colony formation, EdU proliferation), and lectin staining. ST6Gal-Ⅰ expression was modulated via shRNA knockdown or overexpression. Mechanistic analyses focused on integrin-β1 (ITGβ1)/FAK/Paxillin signaling and stromal reprogramming. Statistical significance was determined using ANOVA with post hoc tests.</div></div><div><h3>Results</h3><div>ST6Gal-Ⅰ exhibited microenvironment-dependent regulation: low <em>in vitro</em> expression in SRC cells was rescued by stromal co-culture or extracellular matrix (ECM) contact, mirroring high <em>in vivo</em> expression. ST6Gal-Ⅰ overexpression promoted EMT, stemness, angiogenesis, and proliferation. It facilitated MSCs differentiation into cancer-associated fibroblasts (CAFs) via α-SMA/FAP upregulation. Mechanistically, ST6Gal-Ⅰ activated the ITGβ1/FAK/Paxillin axis to enhance cell-ECM adhesion. Silencing ST6Gal-Ⅰ reversed these phenotypes, suppressing malignancy and stromal crosstalk.</div></div><div><h3>Conclusion</h3><div>ST6Gal-Ⅰ is a microenvironment-sensitive driver of SRC progression, orchestrating EMT, stemness, angiogenesis, and stromal reprogramming through ITGβ1/FAK/Paxillin signaling. Its dual role in tumor-autonomous behaviors and stromal co-option highlights its potential as a therapeutic target. Targeting ST6Gal-Ⅰ or downstream effectors (e.g., FAK, CAF-derived signals) may disrupt SRC metastasis and improve clinical outcomes.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103130"},"PeriodicalIF":2.5,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}