Frontiers in bioscience (Landmark edition)最新文献

{"title":"The Potential of Macrophages for Skin Anti-aging.","authors":"Hang Zhou, Yun Wang, Yu-Mei Li, Yun-Wen Zheng","doi":"10.31083/FBL38891","DOIUrl":"https://doi.org/10.31083/FBL38891","url":null,"abstract":"<p><p>Aging is an inevitable reality that every individual has to face. People look forward to intervene and slow down this process, for example, skin anti-aging cosmetic and therapeutic treatments are commercially available in a variety of methods, such as skin tightening and dermal fillers, but these approaches do not fundamentally change the aging state of senescent cells. Fortunately, macrophages possess the capability to promote tissue repair and regeneration, induce angiogenesis, and improve the tissue microenvironment, making their application in the field of skin anti-aging potentially possible. In this review article, we unveiled the features of aged skin, including a reduction in the extracellular matrix, a decrease in vascular density, diminished defense capabilities, and increased inflammation. We then summarized the possible anti-aging functions of macrophages in this field, such as anti-inflammation, immunoregulation, promotion of angiogenesis, and regeneration. We also suggested potential strategies for utilizing macrophages in anti-aging therapies, including recruiting macrophages to the skin, supplying induced macrophages, and regulating macrophage activity. In conclusion, macrophages may play a role in cell therapy for skin anti-aging, though their potential efficacy and mechanisms need to be further explored.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 9","pages":"38891"},"PeriodicalIF":3.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Argon Alleviates Bone Cancer Pain by Mitigating Neuronal Ferroptosis via the TLR2-COX-2 Pathway.","authors":"Peipei Kang, Gujun Cong, Xiaowen Meng, Yang Zhang, Haiyan Sun, Lei Wang, Chao Zhang, Junyi Ma, Tong Liu, Fuhai Ji","doi":"10.31083/FBL43761","DOIUrl":"https://doi.org/10.31083/FBL43761","url":null,"abstract":"<p><strong>Background: </strong>Bone cancer pain (BCP) related neuronal damage is associated with ferroptosis, a regulated cell death dependent on iron. The noble gas argon is known to have neuroprotective effects, reducing neuroinflammation and enhancing neuronal recovery. However, its potential role in alleviating BCP through the modulation of neuronal ferroptosis remains unexplored.</p><p><strong>Methods: </strong>Ferroptosis was induced by Erastin in SH-SY5Y human neuroblastoma cells. Plasmids were used to overexpress or knock down toll-like receptor (<i>TLR</i>) 2 and cyclooxygenase-2 (<i>COX-2</i>). The effects of argon treatment were evaluated in SH-SY5Y cells in which <i>TLR2</i> and <i>COX-2</i> expression was manipulated using viability assays, oxidative stress markers (reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH)), and ferroptosis-related proteins (acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11)). <i>In vivo</i>, a murine BCP model was developed by injecting Lewis lung carcinoma cells into the femoral cavity. Pain behaviors were analyzed, and spinal cord ferroptosis features were evaluated using histology, immunofluorescence, and transmission electron microscopy (TEM).</p><p><strong>Results: </strong><i>In vitro</i> experiments showed that argon treatment restored SH-SY5Y cell viability after Erastin exposure, suppressed ROS and MDA production, and boosted GSH levels. It also downregulated ACSL4 and upregulated GPX4 and SLC7A11. <i>In vivo</i>, argon improved pain behaviors, reduced tumor burden, preserved neuronal integrity, and mitigated ferroptosis-induced damage to the spinal cords of BCP model mice. Argon also significantly suppressed TLR2 and COX-2 expression, disrupting the ferroptosis and inflammation cascades. However, overexpression of TLR2 or COX-2 reversed these protective effects, confirming the pivotal role of the TLR2-COX-2 axis in neuronal ferroptosis and pain modulation.</p><p><strong>Conclusion: </strong>These findings demonstrate that argon effectively mitigates neuronal ferroptosis and alleviates BCP by downregulating the TLR2-COX-2 pathway, highlighting its therapeutic potential for conditions involving ferroptosis, such as cancer-related pain and neurodegenerative diseases.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 9","pages":"43761"},"PeriodicalIF":3.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cystine and Antibiotic Treatment Alters Low Molecular Weight Thiol Levels in <i>Mycobacterium smegmatis</i>.","authors":"Galina Smirnova, Aleksey Tyulenev, Tatyana Kalashnikova, Lyubov Sutormina, Vadim Ushakov, Oleg Oktyabrsky","doi":"10.31083/FBL44441","DOIUrl":"https://doi.org/10.31083/FBL44441","url":null,"abstract":"<p><strong>Background: </strong>Endogenous and exogenous H₂S can influence the virulence of bacteria and their susceptibility to antibiotics and oxidative stress. <i>Escherichia coli</i> and <i>Bacillus subtilis</i>, when grown in minimal medium with sulfate as the sole sulfur source, produce H₂S when treated with cystine or under stress conditions, including exposure to chloramphenicol and ciprofloxacin. However, it is unknown whether <i>Mycobacterium smegmatis</i> is capable of producing sulfide under these conditions and how this production affects cell physiology.</p><p><strong>Methods: </strong>Real-time monitoring of dissolved oxygen (dO₂), pH, extracellular K⁺, and sulfide was performed directly in culture flasks using selective electrodes. Changes in the level of low molecular weight (LMW) thiols were recorded using spectrophotometric methods and high performance liquid chromatography (HPLC).</p><p><strong>Results: </strong>Sudden addition of cystine or chloramphenicol to growing <i>M. smegmatis</i> cultures increased the intracellular level of cysteine and induced its homeostasis mechanisms, which include the export of excess cysteine from cells and its incorporation into mycothiol (MSH), along with desulfurization with H₂S formation. Ciprofloxacin also increased intracellular cysteine concentration and sulfide production but did not induce cysteine release. Both antibiotics inhibited growth and respiration, whereas cystine transiently increased respiration and glucose uptake in <i>M. smegmatis</i>, in contrast to <i>E. coli</i>, which showed a transient inhibition of these processes.</p><p><strong>Conclusions: </strong>The mechanisms of cysteine homeostasis under the action of antibiotics in <i>M. smegmatis</i> are similar to those in <i>E. coli</i> and <i>B. subtilis</i>, indicating the universal nature of stress response. The opposing effects of cystine-derived H₂S on physiological parameters in <i>M. smegmatis</i> and <i>E. coli</i> may be important factors contributing to their susceptibility to antibiotics.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 9","pages":"44441"},"PeriodicalIF":3.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deiodinases' Inhibitors: A Double-Edged Sword.","authors":"Lucia Acampora, Caterina Miro, Annunziata Gaetana Cicatiello, Monica Dentice, Annarita Nappi","doi":"10.31083/FBL40246","DOIUrl":"https://doi.org/10.31083/FBL40246","url":null,"abstract":"<p><p>The deiodinase enzymes are the gatekeepers of the peripheral Thyroid Hormone (TH) metabolism since they catalyze the activation of the prohormone Thyroxine (T4) into the active Triiodothyronine (T3), as well as their inactivation into metabolically inactive forms. Type I and Type II Deiodinases, Type I Deiodinase (D1) and D2, respectively, catalyze the T4-to-T3 conversion, while Type III Deiodinase, D3, terminates the THs action converting T4 into reverse T3 (rT3) and T3 into T2. Deiodinases are sensitive rate-limiting components within the hormonal axis and their enzymatic dysregulation is a common occurrence in several pathological conditions, including cancer. As a result, these enzymes are a potential source of interest for the development of pharmacological compounds exhibiting modulatory effects. The current arsenal of inhibitors for these enzymes is still limited. To date, a significant challenge in the development of deiodinases' inhibitors is the achievement of enzyme selectivity and tissue specificity without disrupting TH regulation in the surrounding healthy tissues. Furthermore, deiodinases were shown to be potent regulators of the neoplastic processes, and their expression is altered in tumors, predisposing to increased aggressiveness and progression toward metastasis. However, especially in the cancer context, this design is complicated by the spatial and temporal heterogeneity of deiodinases expression, expressed as inter-tumoral variability across different cancer types, intra-tumoral variability among distinct tumor regions or cell populations within the same tumor type, and dynamic changes over time. Nevertheless, deiodinases' inhibitors hold promise as a novel class of cancer therapeutics. Here, we proposed an overview of the actual knowledge of deiodinases' inhibitors, highlighting their potentials and limitations. Future research should focus on identifying the most effective inhibitors, refining delivery mechanisms, and optimizing treatment regimens to minimize side effects while maximizing therapeutic efficacy.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 9","pages":"40246"},"PeriodicalIF":3.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insight into the Mechanism of Action of Prokaryotic SSB Interactomes.","authors":"Piero R Bianco, Cheng-Yang Huang","doi":"10.31083/FBL36350","DOIUrl":"https://doi.org/10.31083/FBL36350","url":null,"abstract":"<p><p>To maintain genome stability, the coordinated actions of multiple proteins and protein complexes, which are collectively known as genome guardians, are required. In prokaryotes, one such 20-member genome guardian family known as the single-stranded DNA binding protein (SSB) interactome exists. Proteins within this essential family contain oligonucleotide/oligosaccharide-binding folds (OB-fold). These structurally conserved OB-folds bind to the intrinsically disordered linkers characteristic of SSB protein C-termini, resulting in partner regulation. The mechanism of binding employed is similar to that utilized by Src homology 3 domain (SH3) proteins in eukaryotes. Binding requires the interaction of conserved PXXP motifs in the SSB linker with the OB-fold in the partner. A second region of SSB C-termini, an 8-10 stretch of predominantly acidic amino acids functions to maintain the linker domain in a biologically active conformation, while simultaneously preventing it from adhering to the OB-folds of the SSB tetramer from which it emanates. In addition, this acidic domain also functions as a secondary binding site docking with a distal site in the partner, stabilizing the linker/OB-fold interactions. The interaction of an SSB with its partner proteins is genus-specific and results in the loading of partners onto the genome at various stages of the cell cycle thereby maintaining genome stability.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 9","pages":"36350"},"PeriodicalIF":3.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of m6A Modification in Regulating MSC Differentiation and Immunomodulation: Implications for Regenerative Medicine and Therapeutic Applications.","authors":"Junhui Zhao, Xiaoyun Zhang, Yanhui Wang, Yu Zeng, Hongliang Sun, Xiaodong Cui","doi":"10.31083/FBL36475","DOIUrl":"https://doi.org/10.31083/FBL36475","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) are widely utilized in tissue repair, anti-inflammatory treatment, and cell therapy due to their remarkable multidirectional differentiation potential, immunosuppressive capabilities, and low immunogenicity. However, the regulatory mechanisms underlying their functions are intricate, and epigenetic modifications are a significant contributing factor. N6-methyladenosine (m6A) modification affects the proliferation, differentiation, and immunomodulation of MSCs by regulating the stability, transport, and translation of RNA. Studies have shown that m6A modification promotes osteogenic differentiation through the bone morphogehetic protein/small mothers against decapentaplegic (BMP/Smad) and wingless-related integration site/β-catenin (Wnt/β-catenin) pathways. It also enhances the anti-inflammatory effect of MSCs by modulating immune cell polarization and the release of inflammatory mediators. Moreover, exosomes secreted by MSCs contribute to immunomodulation and the response to cancer treatment by regulating the m6A modification of genes in target cells. \"Writers\" of m6A, such as methyltransferase-like 3 (METTL3) and METTL14, and \"erasers\", such as fat mass and obesity-associated protein (FTO) and alkB homolog 5 (ALKBH5), are crucial in regulating the functions of MSCs. Targeting m6A modification via the clinical application of MSCs may represent a new cancer treatment strategy. Therefore, a comprehensive investigation of the m6A regulatory mechanism is essential. This review provides theoretical and technical support for the clinical use of MSCs, facilitating the development of more effective therapeutic strategies.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 9","pages":"36475"},"PeriodicalIF":3.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One Size Does Not Fit All: Precision Combinations for FGFR4-driven Cancers.","authors":"Emmy D G Fleuren","doi":"10.31083/FBL43996","DOIUrl":"https://doi.org/10.31083/FBL43996","url":null,"abstract":"<p><p>Oncogenic FGFR4 signalling represents an attractive therapeutic target across multiple cancers, yet treatment resistance almost uniformly occurs. A critical mechanism steering resistance is a rapid and complex reprogramming of kinase signalling networks, called the adaptive bypass response. Capturing this dynamic rewiring to pinpoint, on a molecular level, the right combinatorial drug for the right FGFR4-driven cancer patient at the right time, will be key to achieving sustained tumour responses. But how can one accurately capture this process across different cancer types exhibiting contrasting levels of FGFR4 signalling pathway components and network behaviours? A recent study by Shin <i>et al</i>. delivers a technically elegant and biologically grounded exploration of the adaptive signalling landscape to tackle this, revealing cell context-dependent combinatorial strategies.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 9","pages":"43996"},"PeriodicalIF":3.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PTTG1IP Orchestrates Epithelial-Mesenchymal Transition and DNA Damage Response in Thyroid Cancer Progression.","authors":"Henglu Zhang, Li Zhou, Suyu Wang, Di Yao, Jun Ma, Xiaoyan Hu, Wencheng Zhang, Mengyuan Tao, Min Wang, Weiping Lu","doi":"10.31083/FBL44789","DOIUrl":"https://doi.org/10.31083/FBL44789","url":null,"abstract":"<p><strong>Background: </strong>Thyroid cancer progression involves cell-state plasticity in the form of epithelial-mesenchymal transition (EMT), and defects in DNA damage response (DDR), both of which are linked to metastasis and treatment failure. The role of pituitary tumor transforming 1 interacting protein (PTTG1IP/PBF) in these processes remains insufficiently defined.</p><p><strong>Methods: </strong>Transcriptomes from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) (GSE138042) datasets were analyzed to prioritize EMT-associated genes and to assess correlations with EMT regulators, junction markers, and matrix metalloproteinases. PTTG1IP expression was measured by quantitative real-time reverse transcriptase PCR (qRT-PCR) in thyroid cancer cell lines and normal thyroid HTori-3 cells. Cell viability (Cell Counting Kit-8 (CCK-8)) and apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling, TUNEL) assays were performed following shRNA knockdown of PTTG1IP. The PTTG1IP-CTTN association was examined by co-immunoprecipitation and immunofluorescence. Chromatin immunoprecipitation (ChIP)-qPCR was used to investigate PTTG1IP occupancy at DDR gene promoters. Radiosensitivity was evaluated by loss of cell viability, flow-cytometric cell death, and phosphorylated H2AX (p-H2AX) immunofluorescence after irradiation.</p><p><strong>Results: </strong>PTTG1IP emerged as a top EMT-linked candidate across cohorts, with elevated mRNA and protein expression in thyroid cancers and cell lines. Silencing of PTTG1IP reduced viability and increased apoptosis in human thyroid cancer cell lines TPC-1 and KTC-1. PTTG1IP expression aligned with canonical EMT transcription factors and with DDR genes. Biochemically, PTTG1IP formed an endogenous complex with cortactin (CTTN) and co-localized in cancer cells. Mechanistically, PTTG1IP occupied the BRCA1, BRCA2, RAD51, RAD51-associated protein 1 (RAD51AP1), and ATM serine/threonine kinase (ATM) promoters. Functionally, depletion of PTTG1IP led to increased radiation-induced DNA damage and cell death, resulting in a greater post-irradiation loss of viability.</p><p><strong>Conclusions: </strong>PTTG1IP is a multifunctional node in thyroid cancer, coupling cytoskeletal programs with DDR control, and supporting cell growth and treatment tolerance. The targeting of PTTG1IP, particularly to enhance radiosensitivity, may provide a novel therapeutic strategy for thyroid cancer.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 9","pages":"44789"},"PeriodicalIF":3.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of <i>MYC</i> in Tumor Immune Microenvironment Regulation: Insights and Future Directions.","authors":"Bikesh K Nirala, Jason T Yustein","doi":"10.31083/FBL37304","DOIUrl":"https://doi.org/10.31083/FBL37304","url":null,"abstract":"<p><p>Cancer continues to be a significant global health issue, influenced by genetic mutations and external factors like carcinogenic exposure, lifestyle choices, and chronic inflammation. The myelocytomatosis (<i>MYC</i>) oncogene family, including <i>c-MYC</i>, <i>MYCN</i>, and <i>MYCL</i>, is essential in the development, progression, and metastasis of various cancers such as breast, colorectal, osteosarcoma, and neuroblastoma. Beyond its well-known roles in cell growth and metabolism, <i>MYC</i> significantly shapes the tumor immune microenvironment (TIME) by altering immune cell dynamics, antigen presentation, and checkpoint expression. It contributes to immune evasion by upregulating checkpoints such as programmed death-ligand 1 (PD-L1) and cluster of differentiation (CD)47, suppressing antigen-presenting major histocompatibility complex (MHC) molecules, and promoting the recruitment of suppressive immune cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). While direct targeting of <i>MYC</i> has proven challenging, recent advances in therapeutic strategies, including MYC-MYC-associated factor X (MAX) dimerization inhibitors, bromodomain and extra terminal domain (BET) and cyclin dependent kinase (CDK) inhibitors, synthetic lethality approaches, and epigenetic modulators, have shown promising results in preclinical and early clinical settings. This review discusses <i>MYC</i>'s comprehensive impact on TIME and examines the promising therapeutic strategies of <i>MYC</i> inhibition in enhancing the effectiveness of immunotherapies, supported by recent preclinical and clinical findings.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 9","pages":"37304"},"PeriodicalIF":3.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microenvironment of Solid Tumors.","authors":"Tatyana V Korneenko, Nikolay B Pestov, Mikhail I Shakhparonov, Nickolai A Barlev","doi":"10.31083/FBL36940","DOIUrl":"https://doi.org/10.31083/FBL36940","url":null,"abstract":"<p><p>The tumor microenvironment (TME) plays a fundamental role in tumor progression. Cancer cells interact with their surroundings to establish a supportive niche through structural changes and paracrine signaling. Cells around transformed tumor cells contribute to cancer development, while infiltrating immune cells in this aggressive TME often become exhausted. Solid tumors, especially the most invasive types such as pancreatic ductal adenocarcinoma, are notably stiff mechanically, with cross-linking enzymes significantly affecting the survival of cancer cells in both primary tumors and metastatic sites. In this review, we highlight recent key contributions to the field, focusing on single-cell sequencing of stromal cells, which are increasingly seen as highly heterogeneous yet classifiable into distinct subtypes. These new insights enable the development of effective co-treatment approaches that could significantly enhance current and novel therapies against the most aggressive cancers.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 9","pages":"36940"},"PeriodicalIF":3.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}