Molecular and Cellular Biochemistry最新文献

{"title":"Epigallocatechin 3-gallate-induced neuroprotection in neurodegenerative diseases: molecular mechanisms and clinical insights.","authors":"Md Rezaul Islam, Abdur Rauf, Sumiya Akter, Happy Akter, Md Ibrahim Khalil Al-Imran, Samiul Islam, Meherun Nessa, Chaity Jahan Shompa, Md Nabil Rihan Shuvo, Imtiaz Khan, Waleed Al Abdulmonem, Abdullah S M Aljohani, Muhammad Imran, Marcello Iriti","doi":"10.1007/s11010-025-05211-4","DOIUrl":"10.1007/s11010-025-05211-4","url":null,"abstract":"<p><p>Neurodegenerative diseases (NDs) are caused by progressive neuronal death and cognitive decline. Epigallocatechin 3-gallate (EGCG) is a polyphenolic molecule in green tea as a neuroprotective agent. This review evaluates the therapeutic effects of EGCG and explores the molecular mechanisms that show its neuroprotective properties. EGCG protects neurons in several ways, such as by lowering oxidative stress, stopping Aβ from aggregation together, changing cell signaling pathways, and decreasing inflammation. Furthermore, it promotes autophagy and improves mitochondrial activity, supporting neuronal survival. Clinical studies have demonstrated that EGCG supplementation can reduce neurodegenerative biomarkers and enhance cognitive function. This review provides insights into the molecular mechanisms and therapeutic potential of EGCG in treating various NDs. EGCG reduces oxidative stress by scavenging free radicals and enhancing antioxidant enzyme activity, aiding neuronal defense. It also protects neurons and improves cognitive abilities by inhibiting the toxicity and aggregation of Aβ peptides. It changes important cell signaling pathways like Nrf2, PI3K/Akt, and MAPK, which are necessary for cell survival, cell death, and inflammation. Additionally, it has strong anti-inflammatory properties because it inhibits microglial activation and downregulates pro-inflammatory cytokines. It improves mitochondrial function by reducing oxidative stress, increasing ATP synthesis, and promoting mitochondrial biogenesis, which promotes neurons' survival and energy metabolism. In addition, it also triggers autophagy, a cellular process that breaks down and recycles damaged proteins and organelles, eliminating neurotoxic aggregates and maintaining cellular homeostasis. Moreover, it holds significant promise as an ND treatment, but future research should focus on increasing bioavailability and understanding its long-term clinical effects. Future studies should focus on improving EGCG delivery and understanding its long-term effects in therapeutic settings. It can potentially be a therapeutic agent for managing NDs, indicating a need for further research.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3363-3383"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiogenic Markers in Gestational Diabetes and their Association with Placental Dimensions.","authors":"Shweta Madiwale, Vaishali Kasture, Deepali Sundrani, G V Krishnaveni, Sanjay Gupte, Sadhana Joshi","doi":"10.1007/s11010-024-05189-5","DOIUrl":"10.1007/s11010-024-05189-5","url":null,"abstract":"<p><p>GDM is an increasing global concern, with its etiology not fully understood, though altered placental function is likely to play a role. Placental angiogenesis, essential for sufficient blood flow and nutrient exchange between mother and fetus, may be affected by GDM. However, the role of angiogenic markers in GDM remains unclear. This study aims to investigate angiogenic markers from early pregnancy till delivery and their relationship with placental dimensions. This study is a part of a longitudinal study, where a total of 1154 women were recruited, out of which 167 women developed GDM (15.2%). The current study includes a total of 130 women randomly selected (65 GDM and 65 Non-GDM women). Plasma and placental levels of angiogenic markers such as VEGF, PLGF and sFlt-1/Flt-1 were estimated. Placental dimensions and birth outcomes were recorded, and associations between angiogenic markers and these parameters were examined. sFlt-1 (p < 0.05) levels were higher at V1 (11-14 weeks) in GDM women as compared to Non-GDM women. Placental PLGF (p < 0.01) and Flt-1 (p < 0.05) levels were lower in the GDM group. PLGF and Flt-1 were negatively associated with placental dimensions such as major axis, minor axis and breadth of the placenta. This study reveals altered expression of placental angiogenic markers in women with GDM, potentially affecting placental development and function. Negative correlations between these markers and placental dimensions suggest their influence on pregnancy outcomes in GDM.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3637-3646"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896167","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}

{"title":"METTL3: a multifunctional regulator in diseases.","authors":"Na Li, Xiang Wei, Jian Dai, Jinfeng Yang, Sizheng Xiong","doi":"10.1007/s11010-025-05208-z","DOIUrl":"10.1007/s11010-025-05208-z","url":null,"abstract":"<p><p>N6-methyladenosine (m⁶A) methylation is the most prevalent and abundant internal modification of mRNAs and is catalyzed by the methyltransferase complex. Methyltransferase-like 3 (METTL3), the best-known m⁶A methyltransferase, has been confirmed to function as a multifunctional regulator in the reversible epitranscriptome modulation of m⁶A modification according to follow-up studies. Accumulating evidence in recent years has shown that METTL3 can regulate a variety of functional genes, that aberrant expression of METTL3 is usually associated with many pathological conditions, and that its expression regulatory mechanism is related mainly to its methyltransferase activity or mRNA posttranslational modification. In this review, we discuss the regulatory functions of METTL3 in various diseases, including metabolic diseases, cardiovascular diseases, and cancer. We focus mainly on recent progress in identifying the downstream target genes of METTL3 and its underlying molecular mechanisms and regulators in the above systems. Studies have revealed that the use of METTL3 as a therapeutic target and a new diagnostic biomarker has broad prospects. We hope that this review can serve as a reference for further studies.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3429-3454"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033702","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}

{"title":"Galium verum L. extract mitigates cardiovascular events in psoriasis rats.","authors":"Milena Corbic, Vladimir Jakovljevic, Marina Nikolic, Nevena Jeremic, Jovana Bradic, Jovana Novakovic, Aleksandar Kocovic, Maja Savic, Vanja Tadic, Ana Zugic, Milos Krivokapic, Branislava Daskalovic, Katarina Mihajlovic, Jasmina Sretenovic","doi":"10.1007/s11010-025-05215-0","DOIUrl":"10.1007/s11010-025-05215-0","url":null,"abstract":"<p><p>Psoriasis has been considered a systemic immune-mediated disease that can affect function of the heart. However, certain herbal therapy approaches may nullify side effects of psoriasis on the heart. The aim of this study was to investigate the cardioprotective effects of Galium verum extract administration of the heart of psoriatic rats. The study included 24 Wistar albino male rats, divided into 4 groups: control (CTRL), G.verum (GV), psoriasis (PSORI), and psoriasis with G.verum (PSORI + GV). Seven-day topical application of 5% imiquimod cream was used for induction of psoriasis. After induction, animals were received 125 mg/kg G.verum extract for 4 weeks. Isolated hearts were perfused on the Langendorff apparatus and measured: dp/dt max/min, SLVP, DLVP, HR and coronary flow. The oxidative stress biomarkers: TBARS, NO2, O2- and H2O2 were measured in coronary venous effluent. Isolated hearts were fixed and stained with H/E and Picro-sirius red staining. Psoriasis decreased cardiac contractility and relaxation and increased SLVP and DLVP at all perfusion pressure. Treatment with G.verum in psoriasis rats improved contractility and relaxation of the heart and rise SLVP and DLVP. In PSORI + GV group, the decrease of oxidative stress biomarkers were observed in comparison to PSORI group. Diameter and cross-section area of cardiomyocytes were increased in PSORI and PSORI + GV groups compared to the control. Collagen content was increased in PSORI group by 283% and in PSORI + GV group by 188% compared to control. Treatment with G.verum extract exhibited a positive effect on cardiac function, morphometry and redox state of heart of psoriatic rats.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3783-3798"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080475","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}

{"title":"Altered cognitive function in obese patients: relationship to gut flora.","authors":"Mengyuan Deng, Fushan Tang, Zhaoqiong Zhu","doi":"10.1007/s11010-024-05201-y","DOIUrl":"10.1007/s11010-024-05201-y","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Obesity is a risk factor for non-communicable diseases such as cardiovascular disease and diabetes, which are leading causes of death and disability. Today, China has the largest number of overweight and obese people, imposing a heavy burden on China's healthcare system. Obesity adversely affects the central nervous system (CNS), especially cognitive functions such as executive power, working memory, learning, and so on. The gradual increase in adult obesity rates has been accompanied by a increase in childhood obesity rates. In the past two decades, the obesity rate among children under 5 years of age has increased from 32 to 42 million. If childhood obesity is not intervened in the early years, it will continue into adulthood and remain there for life. Among the potential causative factors, early lifestyle may influence the composition of the gut flora in childhood obesity, such as the rate and intake of high-energy foods, low levels of physical activity, may persist into adulthood, thus, early lifestyle interventions may improve the composition of the gut flora in obese children. Adipose Axis plays an important role in the development of obesity. Adipose tissue is characterized by increased expression of nucleoside diphosphate-linked molecule X-type motif 2 (NUDT2), amphiphilic protein AMPH genes, which encode proteins that all play important roles in the CNS. NUDT2 is associated with intellectual disability. Furthermore, amphiphysin (AMPH) is involved in glutamatergic signaling, ganglionic synapse development, and maturation, which is associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD). All of the above studies show that obesity is closely related to cognitive decline in patients. Animal experiments have confirmed that obesity causes changes in cognitive function. For example, high-fat diets rich in long- and medium-chain saturated fatty acids may adversely affect cognitive function in obese mice. This process may be attributed to the Short-Chain Fatty Acid (SCFA)-rich high-fat diet (HFD) activating enterocyte TLR signaling, especially TLR-2 and TLR-4, altering the downstream MyD88-4 signaling, thereby impacting the downstream MyD88-NF-κB signaling cascade and up-regulating the levels of pro-inflammatory factors and lipopolysaccharide (LPS). These changes result in the loss of integrity of the intestinal mucosa and cause an imbalance in the internal environment. Obesity may lead to the disruption of the intestinal flora and damage the intestinal barrier function, causing intestinal flora dysbiosis. In recent years, a growing number of studies have investigated the relationship between obesity and the intestinal flora. For example, high-fat and high-sugar diets have been found to lead to the thinning of the mucus layer of the colon, a decrease in the number of tight junction proteins, and an increase in intestinal permeability in mice. Such changes alter the composition of intestinal microorganisms, allow endotox","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3553-3567"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of FAP+ fibroblasts on cell proliferation migration and immunoregulation of esophageal squamous carcinoma cells through the CXCL12/CXCR4 axis.","authors":"Lijuan Duan, Shasha Cao, Fang Zhao, Xianjuan Du, Zhaowei Gao, Xiaoxiao Wang, Fang Bian","doi":"10.1007/s11010-025-05226-x","DOIUrl":"10.1007/s11010-025-05226-x","url":null,"abstract":"<p><p>Cancer-associated fibroblasts (CAFs) secrete and synthesize fibroblast activation protein (FAP), which could promote proliferation and immunosuppression of multiple cancers including esophageal squamous cell carcinoma (ESCC). CXCL12/CXCR4 signaling could be revitalized by CAFs in cancer cells. Nevertheless, the significance of this interaction in ESCC has yet to be elucidated. Herein, we investigated whether FAP⁺ CAF cells could promote ESCC cells proliferation, migration and regulate immunity through the CXCL12/CXCR4 pathway in vitro and in vivo. The protein expression level of FSP1, FAP, CD8+ and Ki-67 in different sample was estimated by IHC and western blot. qPCR was used to quantify the mRNA level of FSP1, FAP, CD8+ and Ki-67 in different sample. The cell viability, proliferation, migration and invasion of different sample were evaluated by CCK-8, EdU staining, wound healing assay and Transwell assay, respectively. The ELISA was carried out to measure the protein level of IFN-γ, TNF-α, GZMB and IL-2. ESCC xenograft mice model was established to assess the impact of FAP+ CAF. FSP1, FAP, CD8+ and Ki-67 are greatly up-regulated in hESCC tissues. Through CXCL12/CXCR4 axis, FAP-positive CAF was capable of promoting the cell proliferation, migration and invasion of ESCC tumor cells and preventing the CD8+ T cells from secreting cytokine. Blocking this signaling with selective CXCR4 antagonist could counteract the effects caused by high-expression of FAP. FAP+ CAFs could inhibit the occurrence and development of tumors. These results indicated that FAP-positive CAF have an impact on cell proliferation migration and immunoregulation of ESCC through the CXCL12/CXCR4 axis.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3841-3855"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399211","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}

{"title":"The molecular mechanism by which CTSB degrades FPN to disrupt macrophage iron homeostasis and promote the progression of atherosclerosis.","authors":"Quanli Qiu, Qiyu Sun, Jiaxin Yang, Qingxin Yuan, Ping Wang, Qingwei Liu, Zhenzhen Cui, Xiaowen Ma, Min Li","doi":"10.1007/s11010-025-05228-9","DOIUrl":"10.1007/s11010-025-05228-9","url":null,"abstract":"<p><p>The incidence of atherosclerosis (AS) remains high, and iron-dependent cell death (termed ferroptosis) is thought to play a key role in the progression of AS. Studies have shown that cathepsin B (CTSB) is an important regulatory molecule in atherosclerosis. However, how CTSB regulates AS progression has not been reported, and whether it is related to ferroptosis is poorly studied. In the present study, we observed a significant upregulation of CTSB expression in two AS models, ApoE knockout mice and SD rats given a HFD. According to our findings, CTSB can promote development of the AS plaque region, while inhibition of CTSB showed a reduction of AS lesion area and lipid deposition. Single-cell transcriptome analysis of AS tissue from humans revealed that CTSB is primarily expressed in macrophages. Oxidized low-density lipoprotein (ox-LDL) significantly enhanced macrophage CTSB expression, and induced ferroptosis in vitro. Mechanistically, Ferroportin (FPN) is the binding target of CTSB. CTSB can negatively regulate the protein level of FPN and promote its degradation, which further leads to ferroptosis of macrophages. We confirmed that ferroptosis in macrophages could be effectively inhibited by knockdown or pharmacological inhibition of CTSB, which in turn slowed the progression of AS. In conclusion, our study suggests that CTSB disrupts iron homeostasis in macrophages by degrading FPN and induces ferroptosis, thereby exacerbating the development of AS. Targeting CTSB may become an important potential strategy for the treatment of AS.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3889-3906"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441499","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}

{"title":"The role of resistin and adiponectin ratios with uric acid in assessing metabolic syndrome in type 2 diabetes.","authors":"Almir Fajkić, Orhan Lepara, Rijad Jahić, Malik Ejubović, Avdo Kurtović, Amina Džidić-Krivić, Amira Jagodić Ejubović, Almira Hadžović-Džuvo, Emina Karahmet Sher","doi":"10.1007/s11010-024-05200-z","DOIUrl":"10.1007/s11010-024-05200-z","url":null,"abstract":"<p><p>Metabolic syndrome (MetS) is a growing global healthcare burden. Patients with type 2 diabetes mellitus (T2DM) are more likely to acquire MetS than the general population. Recent research suggests that the interaction of adipose tissue products, such as adiponectin resistin and uric acid, is essential in MetS onset. To examine the role of resistin and adiponectin ratios with uric acid in predicting MetS onset T2DM patients. In a two-year prospective study, 72 T2DM patients were categorised into MetS and non-MetS, according to MetS development. The levels of resistin, adiponectin, uric acid (UA), fasting glucose, high-density lipoprotein cholesterol, and triglycerides were analysed from serum samples. ROC curves and their corresponding areas under the curve (AUC) were utilised to establish the best cut-off values of biomarkers for distinguishing MetS patients and non-MetS patients. The logistic regression analysis was performed to predict the onset of MetS in patients with T2DM. T2DM patients with and without MetS showed significant differences in resistin/UA (p = 0.017), adiponectin/UA (p < 0.001) and adiponectin levels. The Resistin/UA ROC Curve yielded an AUC of 0.825 (p < 0.001), 86.7% sensitivity and 76.2% specificity at a cut-off point of 0.99. Multivariable logistic regression analysis identified resistin /UA ratio [OR 8.631 95% CI 0.450-165.42; p = 0.001] and adiponectin/UA ratio [OR 0.022 95% CI 0.003-0.188; p < 0.001] as independent predictors of MetS. This study confirms the role of resistin-uric acid and adiponectin-uric acid ratios as predictors of MetS development in T2DM patients.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3683-3694"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951626","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}

{"title":"The bone-vascular axis: the link between osteoporosis and vascular calcification.","authors":"Yue Sun, Dageng Huang, Yan Zhang","doi":"10.1007/s11010-025-05210-5","DOIUrl":"10.1007/s11010-025-05210-5","url":null,"abstract":"<p><p>Osteoporosis and vascular calcification are chronic metabolic diseases threatening the health of aging people. The incidence of osteoporosis and vascular calcification increases year by year, and has drawn much attention from the scientific and clinical area. Many studies have found that osteoporosis and vascular calcification are not completely independent, but there are close correlations between them in the pathogenesis and underlying mechanisms. The underlying mechanisms of osteoporosis and vascular calcification include aging, oxidative stress, inflammatory response, lipid metabolism, calcium and phosphorus metabolism, vitamins, autophagy, and extracellular vesicles. This review updates the current understanding of the correlation and underlying mechanisms of osteoporosis and vascular calcification, and highlights the complexity of the bone-vascular axis, aiming to provide novel ideas for the prevention and treatment of osteoporosis and vascular calcification.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3413-3427"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029205","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}

{"title":"Cancer-associated fibroblasts promote growth and dissemination of esophageal squamous cell carcinoma cells by secreting WNT family member 5A.","authors":"Lishuai Yao, Changshuai Zhou, Libao Liu, Jinyuan He, Youbo Wang, An Wang","doi":"10.1007/s11010-025-05223-0","DOIUrl":"10.1007/s11010-025-05223-0","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC) is a common and aggressive subtype of esophageal cancer. This research investigates the functions of cancer-associated fibroblasts (CAFs) in the malignant phenotype of ESCC and probes the underpinning mechanism. Key CAF-associated proteins in ESCC were identified using bioinformatics analyses. ESCC cell lines were co-cultured with CAFs, followed by the addition of neutralizing antibodies against WNT family member 5A (WNT5A) (Anti-WNT5A; AW) and frizzled class receptor 5 (FZD5) (Anti-FZD5; AF), or a human recombinant protein of WNT5A (rWNT5A; rW). The effects of CAF stimulation and the neutralizing or recombinant proteins on the growth and dissemination of ESCC cells were investigated. In addition, ESCC cells were transplanted into nude mice for in vivo assessment of tumor growth and metastasis. WNT5A was identified as a CAF-associated protein linked to poor prognosis in ESCC. Co-culturing with CAFs augmented proliferation, mobility, and apoptosis resistance of ESCC cells. These effects were negated by the AW or AF but restored by rW. WNT5A interacted with FZD5 to activate the WNT signaling in ESCC cells. The rW treatment also enhanced tumorigenesis and metastasis of xenograft tumors in nude mice, with these effects diminished by AW or AF treatment. This study suggests that CAFs promote growth and dissemination of ESCC cell primarily through the secretion of WNT5A.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"3857-3872"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425853","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}