JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"PTBP1 and Cancer: From RNA Regulation to Therapeutic Potential","authors":"Chengdong Ji,&nbsp;Jing Zhu,&nbsp;Xiaochen Hou,&nbsp;Chen Zhou,&nbsp;Jiumei Zhao,&nbsp;Xiang Zheng,&nbsp;Yu Tang","doi":"10.1111/jcmm.70675","DOIUrl":"https://doi.org/10.1111/jcmm.70675","url":null,"abstract":"<p>Polypyrimidine tract binding protein 1 (PTBP1) belongs to the heterogeneous nuclear ribonucleoprotein (hnRNP) family and is a widely studied RNA-binding protein involved in regulating mRNA splicing, stability, localization, and translation. In addition, PTBP1 can participate in various non-coding RNA action processes and affect tumorigenesis and progression. In tumour therapy, PTBP1 may act as a key factor influencing targeted drug targets. Therefore, in this paper, we reviewed the structure and function of PTBP1, its role in various tumours, and key mechanisms of action. Moreover, we discuss the difficulties and challenges faced in PTBP1 research and the clinical translational potential of PTBP1 research and summarise the future research direction of PTBP1 to provide new ideas for basic research and new directions for precision treatment of tumours in the clinic.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 13","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70675","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabidiol Is a Potential Inhibitor of Ferroptosis in Human Articular Chondrocytes","authors":"A. Wipplinger,&nbsp;D. Bekric,&nbsp;C. Ablinger,&nbsp;M. Kittl,&nbsp;C. Mayr,&nbsp;M. Ritter,&nbsp;M. Winklmayr,&nbsp;M. Jakab","doi":"10.1111/jcmm.70592","DOIUrl":"https://doi.org/10.1111/jcmm.70592","url":null,"abstract":"<p>The present study investigates the effects of cannabidiol (CBD), the major non-psychoactive compound of <i>Cannabis sativa</i> L. extracts, on ferroptotic cell death in human articular chondrocytes. Exposure to known ferroptosis inducers RSL3, erastin and its analogue IKE, FINO2 and FIN56 led to a varying extent of reduced cell viability in two chondrocyte cell lines (in C-28/I2, T/C-28/A2) and primary chondrocytes, suggesting different sensitivity and defence mechanisms towards the respective substances. The cytotoxic effects were aggravated by additional exposure to iron and inhibited by the specific ferroptosis inhibitor ferrostatin-1 (Fer-1), proving the occurrence of ferroptosis. Strikingly, co-treatment of ferroptosis inducers with CBD clearly restored cell viability in a dose-dependent manner (10 nM to 1 μM CBD) in both cell lines and primary chondrocytes. Moreover, CBD restored the activity of GPX4, a major anti-oxidative enzyme, to varying degrees when combined with IKE or RSL3. Increasing evidence has emerged for an important role of iron dyshomeostasis and ferroptosis in the onset and progression of various orthopaedic diseases, including osteoarthritis. Therefore, the here demonstrated and previously unreported cytoprotective and anti-oxidative effects of CBD in the context of ferroptosis have highly promising therapeutic implications.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 13","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70592","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Immunity to Oncology: Itaconic Acid as a Driver in HBV-Induced HCC","authors":"Shahab Mahmoudvand,&nbsp;Sheida Behzadi Sheikhrobat,&nbsp;Somayeh Shokri,&nbsp;Hossein Bannazadeh Baghi","doi":"10.1111/jcmm.70612","DOIUrl":"https://doi.org/10.1111/jcmm.70612","url":null,"abstract":"&lt;p&gt;Itaconic acid (ITA) is an immunomodulatory mammalian metabolite secreted from primary macrophages that dramatically increases upon activation. The metabolite plays a significant role in epigenetic regulation, influencing immune responses and disease progression. In recent years, ITA has gained attention due to its anti-microbial and immunomodulatory activities [&lt;span&gt;1&lt;/span&gt;]. However, the ‘yin and yang’ role of itaconate should not be overlooked because it can promote tumour growth [&lt;span&gt;2&lt;/span&gt;]. This letter offers an overview of ITA's epigenetic role, which may provide new strategies for treating hepatocellular carcinoma (HCC), particularly in patients infected with the hepatitis B virus (HBV). The interplay between HBV and host epigenetic mechanisms is crucial in developing HCC, suggesting that interventions targeting these pathways could be beneficial.&lt;/p&gt;&lt;p&gt;ITA has been identified as a modulator of histone modifications, particularly through a process known as lysine itaconylation. This modification plays a significant role in various biological processes, including immune responses and cancer progression [&lt;span&gt;3&lt;/span&gt;]. Itaconate promotes the expression of immune checkpoint proteins like programmed cell death protein 1 (PD-1) and T cell immunoglobulin and mucin domain 3 (TIM-3) by enhancing histone modifications at the Eomesodermin (EOMES) promoter, contributing to CD8&lt;sup&gt;+&lt;/sup&gt; T-cell exhaustion in HCC [&lt;span&gt;4&lt;/span&gt;]. Research indicates that itaconate promotes CD8&lt;sup&gt;+&lt;/sup&gt; T-cell exhaustion via epigenetic induction, which may exacerbate HCC development in HBV-infected individuals. Thimme et al. [&lt;span&gt;5&lt;/span&gt;] recently explained that CD8&lt;sup&gt;+&lt;/sup&gt; T cells are crucial in controlling HBV infection but are functionally impaired during chronic HBV infection.&lt;/p&gt;&lt;p&gt;CD8+ T cells play a crucial role in the context of HBV infection. Specifically, during acute-resolving HBV infection, these cells serve as the primary effector cells that facilitate viral clearance and contribute to the pathogenesis of the disease. CD8+ T cell exhaustion refers to impaired function and diminished numbers of T cells, significantly contributing to advancing HBV infection [&lt;span&gt;6&lt;/span&gt;]. Recent progress in exploring exhausted T cells during chronic HBV infection has provided novel insight into the possibility of immunotherapy for this disease [&lt;span&gt;7&lt;/span&gt;]. Gu et al. demonstrated an epigenetic connection between itaconate and HCC, indicating that focusing on immune-responsive gene 1 (IRG1), which is responsible for the synthesis of itaconate, or on itaconate itself could represent a promising approach for the treatment of HCC. Furthermore, combining T-cell and anti-PD1 therapy may offer potential curative effects [&lt;span&gt;4&lt;/span&gt;]. Conversely, while lysine itaconylation presents a promising area of research, the complexity of viral interactions with host modifications indicates that further studies are necessary to elucidate its specific role in H","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 12","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70612","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Pan-Cancer Study of Tumour-Associated Efferocytosis Core Genes and Preliminary Exploration of TIMD4 in Renal Cell Carcinoma","authors":"Hongze Li,&nbsp;Jiaqi Zhang,&nbsp;Yixiao Zhang,&nbsp;Zixuan Li,&nbsp;Yuxi Han,&nbsp;Yu Lun","doi":"10.1111/jcmm.70671","DOIUrl":"https://doi.org/10.1111/jcmm.70671","url":null,"abstract":"<p>Efferocytosis plays a crucial role in maintaining the stability of the immune microenvironment. Increasing research indicates that efferocytosis core genes (ECGs) are not only widely expressed in immune cells, but also expressed at significant levels in tumour cells, impacting tumour progression. However, the comprehensive effects of ECGs on cancer prognosis and the immune microenvironment remain underexplored. This study analysed data from 33 tumour types to assess the expression, diagnostic and prognostic values of ECGs as well as gene modification landscapes. It also predicted the correlation between ECGs, the immune microenvironment and responses to immunotherapy, revealing that lower ECGs expression levels were associated with better immunotherapy responses in various cancers. Additionally, molecular docking studies simulated the interactions between TIMD4 and its sensitive drugs, facilitating targeted drug development. Finally, both in vitro and in vivo experiments confirmed that silencing TIMD4 could effectively inhibit the proliferation and invasion of renal cell carcinoma. Overall, TIMD4 can be used as an important biomarker for tumour prognosis and immunotherapy response, providing new insights into the mechanisms of tumour immune microenvironment and progression, as well as a novel therapeutic target.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 12","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70671","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactylation-Related Gene LILRB4 Predicts the Prognosis and Immunotherapy of Prostate Cancer Based on Machine Learning","authors":"Qinghua Wang,&nbsp;Xin Qin,&nbsp;Yan Zhao,&nbsp;Wei Jiang,&nbsp;Mingming Xu,&nbsp;Xilei Li,&nbsp;Haopeng Li,&nbsp;Juan Zhou,&nbsp;Gang Wu","doi":"10.1111/jcmm.70669","DOIUrl":"https://doi.org/10.1111/jcmm.70669","url":null,"abstract":"<p>Lactylation plays a pivotal role in the metabolic reprogramming, proliferation, migration and immune evasion of tumour cells. However, its specific impact on prostate cancer (PCa) remains poorly understood. This study aimed to investigate the role of lactylation related genes (LRGs) in PCa. LRGs were identified and analysed using data from The Cancer Genome Atlas (TCGA), DKFZ2018, GSE46602 and GSE70768 cohorts. Unsupervised clustering was employed to categorise patients with PCa into two distinct clusters. Prognostic models for PCa were developed using multiple machine learning techniques. LRGs signature was established and validated through training and validation sets. The role of leukocyte immunoglobulin-like receptor B4 (LILRB4) in PCa was examined both in vitro and in vivo. Analysis of LRG expression and prognosis in patients with PCa revealed two distinct clusters with differing survival rates and immune responses. Machine learning models demonstrated the ability to predict survival risks, potentially aiding in the development of personalised treatment strategies. Additionally, LILRB4, a key LRG, promotes PCa progression by modulating the NF-κB and PI3K/AKT pathways, highlighting its potential as a therapeutic target. LRGs exert a pivotal influence on PCa, impacting patient prognosis, immune response and drug sensitivity. The LRGs signature emerges as an essential prognostic tool and a promising therapeutic target for PCa.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 12","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70669","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hippo Pathway Regulates Cell Proliferation in Skin Epidermis Exposed to Mechanical Forces","authors":"Joanna K. Ledwon,&nbsp;Bianka Progri,&nbsp;Sarah A. Applebaum,&nbsp;Oveyaa Vignesh,&nbsp;Alice Yau,&nbsp;Angie H. Aguilar,&nbsp;Adrian B. Tepole,&nbsp;Arun K. Gosain","doi":"10.1111/jcmm.70674","DOIUrl":"https://doi.org/10.1111/jcmm.70674","url":null,"abstract":"<p>Tissue expansion is an integral component of reconstructive surgery used to promote native skin growth. This process is driven by the gradual inflation of the tissue expander placed subcutaneously on the patient's body. Despite its widespread use, the lack of in vivo evidence on the biological processes underlying skin growth has limited technological advancements. Here, we explore the gene and protein expression changes that control mechanically induced skin growth during tissue expansion. Using a porcine tissue expansion model, we revealed that skin expansion disrupts key components responsible for epithelial integrity, as evidenced by the loss of E-cadherin and alpha-catenin expression in expanded skin compared to the unexpanded control. This disruption correlates with the translocation of the transcriptional factor YAP1 from the membrane to the nucleus, activating keratinocyte proliferation and possibly regulating other critical processes involved in skin adaptation to mechanical stretch. Our data show that in vivo cell proliferation is mediated by force-induced changes in the composition of molecular complexes formed by E-cadherin, alpha-catenin, and YAP1.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 12","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70674","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VHL-Mediated SYT11 Degradation Suppresses Gastric Cancer Cell Growth and Invasion Through Downregulation of SPINK1","authors":"Ji Su Yu,&nbsp;Mi-Aie Hwang,&nbsp;Misun Won,&nbsp;Joo-Young Im,&nbsp;Dae-Hyuk Kweon,&nbsp;Yun Gyu Park,&nbsp;Bo-Kyung Kim","doi":"10.1111/jcmm.70658","DOIUrl":"https://doi.org/10.1111/jcmm.70658","url":null,"abstract":"<p>The ubiquitin-proteasome system is a post-translational modification pathway that plays a critical role in regulating cell survival and death. E3 ubiquitin ligases are key tumour regulators and potential therapeutic targets in gastric cancer. This study investigates whether von Hippel–Lindau (VHL), an E3 ligase, regulates the stability of synaptotagmin 11 (SYT11) protein in gastric cancer cells. VHL overexpression decreased SYT11 protein expression without affecting SYT11 mRNA expression. Notably, VHL overexpression decreased the half-life of SYT11 protein, and MG132, a proteasome inhibitor, reversed SYT11 degradation by VHL. Immunoprecipitation confirmed the binding of SYT11 to VHL, and VHL knockdown resulted in reduced SYT11 ubiquitination and degradation. Transcriptome sequencing revealed the downregulation of serine peptidase inhibitor kazal type 1 (SPINK1) by VHL and its upregulation by SYT11. VHL downregulated the expression of SYT11, which subsequently led to the inhibition of SPINK1 expression. Furthermore, SPINK1 knockdown inhibited the growth and invasion of gastric cancer cells, mirroring VHL overexpression effects. The inhibition of growth and invasion in MKN1 and SNU484 cells by VHL was rescued by the overexpression of SYT11 and SPINK1. These findings demonstrate that the proteasome-dependent degradation of SYT11 by VHL and the subsequent reduction in SPINK1 expression inhibit gastric cancer cell growth and invasion.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 13","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70658","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DPP7 Promotes Colorectal Cancer Progression Through GPX4-Dependent Suppression of Disulfidptosis and Immune Evasion","authors":"Ruibing Li,&nbsp;Xinyou Wang,&nbsp;Jun Liu,&nbsp;Zeyu Cai,&nbsp;Zhu Li,&nbsp;Qiang Tao,&nbsp;Chong Wang","doi":"10.1111/jcmm.70660","DOIUrl":"https://doi.org/10.1111/jcmm.70660","url":null,"abstract":"<p>Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, highlighting the need to identify novel mechanisms driving tumour progression. In this study, we demonstrate that dipeptidyl peptidase 7 (DPP7) high expression correlates with poor prognosis in CRC patients. Functional analyses revealed that DPP7 promotes CRC cell proliferation and inhibits apoptosis, while its depletion enhances natural killer (NK) cell-mediated cytotoxicity against tumour cells. Mechanistically, we identified a previously unknown role of DPP7 in suppressing disulfidptosis, a novel form of regulated cell death characterised by excessive formation of intracellular disulfide bonds. DPP7 overexpression protected CRC cells from glucose deprivation-induced disulfidptosis, as evidenced by reduced disulfide bond formation in cytoskeletal proteins including drebrin, FLNA and FLNB. Furthermore, we discovered that DPP7 physically interacts with glutathione peroxidase 4 (GPX4), a key regulator of cellular redox homeostasis, and stabilises GPX4 protein without affecting its mRNA expression. GPX4 restoration in DPP7-depletion cells reversed the enhanced sensitivity to both disulfidptosis and NK cell-mediated killing, while GPX4 depletion abolished the protective effect of DPP7 overexpression. Our findings unveil a novel DPP7-GPX4 axis in regulating disulfidptosis and immune evasion in colorectal cancer, providing potential therapeutic targets for CRC treatment. Targeting this pathway may simultaneously inhibit tumour cell survival mechanisms and enhance immune-mediated tumour elimination.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 12","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70660","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of a Prognostic Model Using RNA Processing Factor Genes and the Key Role of NSUN6 in Glioma Outcomes","authors":"Jiarui Chen,&nbsp;Caidi Ying,&nbsp;Zhaowen Gu,&nbsp;Bingrui Zhu,&nbsp;Junjie Wang,&nbsp;Yajun Qian,&nbsp;Haiyan Zheng,&nbsp;Jianming Zhang,&nbsp;Yongjie Wang","doi":"10.1111/jcmm.70668","DOIUrl":"https://doi.org/10.1111/jcmm.70668","url":null,"abstract":"<p>Glioma is the most common malignant brain tumor and remains associated with a poor prognosis and limited predictive tools. The dysregulation of RNA processing factor genes has been implicated in glioma development, yet their prognostic relevance remains unclear. This study aimed to construct a robust prognostic model based on RNA processing factor genes and explore their functional roles and therapeutic potential. Transcriptomic and clinical data from glioma patients in the TCGA, CGGA, GEO and Rembrandt cohorts were analysed. Univariate, multivariate and LASSO-Cox regression analyses were performed to establish a prognostic signature. Model performance was assessed using Kaplan–Meier survival curves, time-dependent ROC analysis and C-index evaluation. Key genes were identified via random forest analysis and validated through single-cell datasets and immunohistochemistry. Functional assays were conducted to examine the biological roles of the key gene. Seventy-eight RNA processing factor genes were associated with glioma prognosis, and a 19-gene risk signature was constructed. The model effectively stratified patients into high- and low-risk groups with significantly different survival outcomes (log-rank <i>p</i> &lt; 0.001). The AUCs for 1-, 3- and 5-year survival were 0.812, 0.774 and 0.769 in TCGA and 0.796, 0.758 and 0.741 in CGGA. The model achieved a C-index of 0.781 and was validated as an independent prognostic factor. NSUN6 was identified as a key protective gene whose overexpression inhibited glioma cell proliferation and migration in vitro. RNA processing factor genes have prognostic utility in glioma. The 19-gene model and NSUN6 highlight novel avenues for molecular stratification and targeted therapy.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 12","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70668","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-Dependent Effects of Low-Intensity Pulsed Ultrasound on Apoptosis and Autophagy in Malignant Melanoma Stem Cells","authors":"Omer Dikici,&nbsp;Berrin Ozdil,&nbsp;Taha Kadir Yesin,&nbsp;Aylin Dikici,&nbsp;Yasemin Adalı,&nbsp;Huseyin Aktug","doi":"10.1111/jcmm.70687","DOIUrl":"https://doi.org/10.1111/jcmm.70687","url":null,"abstract":"<p>Cancer stem cells (CSCs) in malignant melanoma contribute to therapeutic resistance and tumour recurrence. While low-intensity pulsed ultrasound (LIPUS) has been proposed as a non-invasive strategy to induce cell death, its effects on CSC-specific apoptotic and autophagic responses remain unclear. This study aimed to explore the time-dependent effects of LIPUS on apoptosis and autophagy in CD133+ melanoma CSCs and CD133− non-stem melanoma cells. Human melanoma cells (CHL-1) were sorted via FACS into CD133+ and CD133− populations. Cells were exposed to LIPUS (1 MHz, 20% duty cycle, 1 W/cm²) for 1, 5, and 10 min. Protein expression levels of Caspase-3, Caspase-8, mTOR, and LC3 were evaluated via immunofluorescence and quantified by image-based analysis. Both cell populations showed significant increases in Casp3, Casp8, mTOR, and LC3 intensities following LIPUS application. Notably, CD133+ cells exhibited delayed but sustained increases in Casp3 and LC3 expression, while CD133− cells responded more rapidly. mTOR activity demonstrated distinct temporal dynamics between the two groups, suggesting differential modulation of autophagy-related pathways. LIPUS triggers temporally distinct apoptotic and autophagic responses in melanoma CSCs and non-stem cancer cells. These findings suggest a potential therapeutic avenue to selectively disrupt CSC survival mechanisms using mechanical stimulation.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 12","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70687","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}