Cellular & Molecular Biology Letters最新文献

{"title":"AFM reveals differential effects of acidification on LDL- and oxidized LDL-receptor interactions: biomechanical implications in atherogenesis.","authors":"Kun Wang, Chenhan Sun, Hongda Zhuang, Xian-Cheng Jiang, Yong Chen","doi":"10.1186/s11658-025-00715-9","DOIUrl":"https://doi.org/10.1186/s11658-025-00715-9","url":null,"abstract":"<p><p>The receptor recognition and interaction of plasma lipoproteins (e.g., native low-density lipoproteins (LDL)/oxidized low-density lipoproteins (oxLDL), as well as the influence of microenvironmental/lysosomal acidification, play critical roles in lipoprotein metabolism and diseases (e.g., atherosclerosis) but have been less investigated. Here, the recognition/interaction of LDL or oxLDL with LDL receptor (LDLR) or CD36 (a scavenger receptor) or with living cells at various pHs was evaluated mainly via atomic force microscopy (AFM). To improve force measurement accuracy, a novel, micro-droplet-based method for AFM probe functionalization was developed. We found that solution acidification significantly reduced the LDL-LDLR binding at pH ≤ 6.4, whereas the oxLDL-CD36 binding had no significant change until pH ≤ 4.4. Compared with a traditional immersion method, our micro-droplet method for AFM probe functionalization produced more accurate interaction forces, and revealed that acidification significantly reduced the LDL-LDLR/cell interaction forces, instead of the oxLDL-CD36/cell-specific interaction forces and nonspecific interaction forces. The data imply that the LDL-LDLR/cell recognition and interaction are susceptible to acidification, whereas the oxLDL-CD36/cell recognition and interaction are tolerant of acidification. The results may provide important novel information and biomechanical/pathological implications for understanding lipoprotein metabolism and atherosclerosis.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"32"},"PeriodicalIF":9.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering distinct spatial alterations in N-glycan expression profiles in the spinal cord and brain of male rats in a neuropathic pain model.","authors":"Hyun Jun Jang, Juhee Shin, Sangkyu Lee, Boyoung Lee, Dong Woon Kim","doi":"10.1186/s11658-025-00709-7","DOIUrl":"10.1186/s11658-025-00709-7","url":null,"abstract":"<p><strong>Background: </strong>Neuropathic pain is a complex condition resulting from damage or disease in the somatosensory nervous system, causing significant physical and emotional distress. Despite its profound impact, the underlying causes and treatment methods of neuropathic pain remain poorly understood.</p><p><strong>Methods: </strong>To better understand this condition, we conducted the first study examining the spatial distribution and dynamic expression changes of N-glycan molecules that play a crucial role in nervous system function and sustainable pain signal transmission across multiple regions of the spinal cord and brain in an experimentally induced neuropathic pain model, using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI).</p><p><strong>Results: </strong>Our findings revealed that neuropathic pain induces dynamic changes in N-glycan expression across various regions of the spinal cord and brain. Notably, we discovered distinct glycan profiles between the spinal cord and brain, with N-glycans downregulated in the spinal cord and upregulated in the brain at a time when mechanical allodynia is sustained following spinal nerve ligation (SNL). Significant changes in N-glycan expression were observed in the dorsal laminae IV/V/VI and the ventral horn of the spinal cord. Additionally, marked changes were detected in the contralateral regions of the primary sensory cortex (S1) and the primary sensory cortex hindlimb area (S1HL). Furthermore, we observed significant upregulation of N-glycan expression in the thalamus, anterior cingulate cortex (ACC), and medial prefrontal cortex (mPFC) in both ipsilateral and contralateral regions of the brain.</p><p><strong>Conclusions: </strong>Given that N-glycans are implicated in pain processing yet their precise role remains unclear, our study highlights the need to explore N-glycosylation with a more nuanced focus on both the spinal cord and brain. This research provides new insights into the mechanisms of persistent neuropathic pain and lays the groundwork for future studies and the development of targeted therapeutic strategies.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"31"},"PeriodicalIF":9.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SWI/SNF-type complexes-transcription factor interplay: a key regulatory interaction.","authors":"Anna Maassen, Jaroslaw Steciuk, Magdalena Wilga, Jakub Szurmak, Damian Garbicz, Elzbieta Sarnowska, Tomasz J Sarnowski","doi":"10.1186/s11658-025-00704-y","DOIUrl":"10.1186/s11658-025-00704-y","url":null,"abstract":"<p><p>ATP-dependent switch/sucrose nonfermenting-type chromatin remodeling complexes (SWI/SNF CRCs) are multiprotein machineries altering chromatin structure, thus controlling the accessibility of genomic DNA to various regulatory proteins including transcription factors (TFs). SWI/SNF CRCs are highly evolutionarily conserved among eukaryotes. There are three main subtypes of SWI/SNF CRCs: canonical (cBAF), polybromo (pBAF), and noncanonical (ncBAF) in humans and their functional Arabidopsis counterparts SYD-associated SWI/SNF (SAS), MINU-associated SWI/SNF (MAS), and BRAHMA (BRM)-associated SWI/SNF (BAS). Here, we highlight the importance of interplay between SWI/SNF CRCs and TFs in human and Arabidopsis and summarize recent advances demonstrating their role in controlling important regulatory processes. We discuss possible mechanisms involved in TFs and SWI/SNF CRCs-dependent transcriptional control of gene expression. We indicate that Arabidopsis may serve as a valuable model for the identification of evolutionarily conserved SWI/SNF-TF interactions and postulate that further exploration of the TFs and SWI/SNF CRCs-interplay, especially in the context of the role of particular SWI/SNF CRC subtypes, TF type, as well as cell/tissue and conditions, among others, will help address important questions related to the specificity of SWI/SNF-TF interactions and the sequence of events occurring on their target genes.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"30"},"PeriodicalIF":9.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CDC20 protects the heart from doxorubicin-induced cardiotoxicity by modulating CCDC69 degradation.","authors":"Zhenyu Feng, Ningning Zhang, Liang Wang, Xumin Guan, Yunpeng Xie, Yun-Long Xia","doi":"10.1186/s11658-025-00708-8","DOIUrl":"10.1186/s11658-025-00708-8","url":null,"abstract":"<p><strong>Aims: </strong>Doxorubicin (DOX) is a potent anticancer drug; however, it is associated with significant cardiotoxicity. CDC20 is an E3 ubiquitin ligase that plays a role in cell cycle progression and apoptosis in various types of cancers. The involvement of CDC20 in DOX-induced cardiotoxicity (DIC) is poorly understood. Hence, this study aimed to explore the potential role of CDC20 in the development of DIC and assess whether CDC20 influences the antitumor effects of DOX.</p><p><strong>Methods and results: </strong>H9C2 cells were treated with DOX, followed by transcriptomic analysis to identify differentially expressed genes. C57BL/6 mice were treated with DOX for 4 weeks after tail vein injection of CDC20 myocardial-specific knockout mice, AAV9-cTNT-(si) CDC20, or intraperitoneal injection of apcin. Cardiac function and pathological changes were evaluated by echocardiography and pathological staining, respectively. The influence of CDC20 on DOX-induced tumor inhibition was assessed in tumor-bearing mice. In vitro analysis involved treating cardiomyocytes with the Ad-CDC20 adenovirus and DOX, followed by proteomic and ubiquitination-related assays to identify potential downstream ubiquitinated CDC20 proteins. Additionally, we investigated the effect of CCDC69 on CDC20-mediated protection against DOX-induced apoptosis using CCDC69 shRNA. Transcriptome analysis revealed that DOX effectively suppressed the expression of CDC20. Cardiomyocyte-specific overexpression of CDC20 in a DOX-induced mouse model of myocardial injury effectively mitigated cardiomyocyte apoptosis, inflammation, fibrosis, and cell atrophy. Our mechanistic investigation revealed that CDC20 attenuates DOX-induced apoptosis by downregulating CCDC69 expression. Moreover, cardiomyocyte-specific overexpression of CDC20 had no effect on the therapeutic efficacy of DOX against tumors.</p><p><strong>Conclusion: </strong>Our findings indicate that CDC20 safeguards the heart against DOX-induced cardiotoxicity by modulating CCDC69 degradation without compromising the antitumor efficacy of DOX.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"29"},"PeriodicalIF":9.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Old drugs, new challenges: reassigning drugs for cancer therapies.","authors":"Paulina Czechowicz, Anna Więch-Walów, Jakub Sławski, James F Collawn, Rafal Bartoszewski","doi":"10.1186/s11658-025-00710-0","DOIUrl":"10.1186/s11658-025-00710-0","url":null,"abstract":"<p><p>The \"War on Cancer\" began with the National Cancer Act of 1971 and despite more than 50 years of effort and numerous successes, there still remains much more work to be done. The major challenge remains the complexity and intrinsic polygenicity of neoplastic diseases. Furthermore, the safety of the antitumor therapies still remains a concern given their often off-target effects. Although the amount of money invested in research and development required to introduce a novel FDA-approved drug has continuously increased, the likelihood for a new cancer drug's approval remains limited. One interesting alternative approach, however, is the idea of repurposing of old drugs, which is both faster and less costly than developing new drugs. Repurposed drugs have the potential to address the shortage of new drugs with the added benefit that the safety concerns are already established. That being said, their interactions with other new drugs in combination therapies, however, should be tested. In this review, we discuss the history of repurposed drugs, some successes and failures, as well as the multiple challenges and obstacles that need to be addressed in order to enhance repurposed drugs' potential for new cancer therapies.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"27"},"PeriodicalIF":9.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"tRF-5028c disrupts trophoblast function in recurrent spontaneous abortion by inhibiting CRKL-mediated Rap1 signaling pathway.","authors":"Jialyu Huang, Jiawei Wang, Shuang Wang, Xiangpeng Xiong, Ruiyin Jiang, Chaoyi Xiong, Lu Wang, Lingling Huang, Yan Zhao, Zheng Fang, Xiaoyan Ai, Jiaying Lin","doi":"10.1186/s11658-025-00706-w","DOIUrl":"10.1186/s11658-025-00706-w","url":null,"abstract":"<p><strong>Background: </strong>Recurrent spontaneous abortion (RSA) affects approximately 1-5% of childbearing women and poses a significant threat to global reproductive health. Transfer RNA-derived small RNAs (tsRNAs) are a novel class of noncoding RNAs implicated in various human diseases. However, the role and mechanism of tsRNAs in regulating trophoblast function during RSA development remain unknown.</p><p><strong>Methods: </strong>High-throughput sequencing was performed to analyze the differential tsRNAs in the villous tissues of patients with RSA and controls. CCK-8, transwell assay, and flow cytometry were performed to detect the effects of tRF-5028c on proliferation, migration, invasion, and apoptosis of human extravillous trophoblast cell line HTR-8/SVneo. The target genes of tRF-5028c were predicted via bioinformatic analysis and verified by dual luciferase reporter gene assay. Moreover, pregnant mice were injected with tRF-5028c mimics to confirm the findings in vivo.</p><p><strong>Results: </strong>A total of 1907 tsRNAs were detected, of which 298 were differentially expressed in the villous tissues. tRF-5028c was significantly upregulated in the RSA group compared with control. Functionally, tRF-5028c overexpression inhibited HTR-8/SVneo cell proliferation, migration, and invasion and promoted apoptosis, whereas tRF-5028c knockdown showed opposite effects. Mechanically, tRF-5028c suppressed CRKL expression by directly binding to its 3'-untranslated region, thus inactivating the downstream C3G/Rap1 signaling pathway. Finally, tRF-5028c mimics injection increased embryo absorption rate in mice.</p><p><strong>Conclusions: </strong>tRF-5028c upregulation impaired trophoblast function to facilitate RSA development by directly targeting CRKL-mediated Rap1 pathway. The findings provide the first evidence of tsRNA dysregulation in RSA pathogenesis and lay a foundation for potential targeted therapies.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"28"},"PeriodicalIF":9.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SRSF3 and hnRNP A1-mediated m6A-modified circCDK14 regulates intramuscular fat deposition by acting as miR-4492-z sponge.","authors":"Chunyu Qin, Fang Xu, Binglin Yue, Jincheng Zhong, Zhixin Chai, Hui Wang","doi":"10.1186/s11658-025-00699-6","DOIUrl":"10.1186/s11658-025-00699-6","url":null,"abstract":"<p><p>The intramuscular fat (IMF) content of yak beef is critical for determining its quality. Circular RNAs (circRNAs) are a group of endogenous non-coding RNAs that have emerged as important factors in the regulation of IMF deposition. However, the molecular mechanisms through which circRNAs regulate IMF deposition, particularly in yaks, remain unclear. In the present study, a novel circRNA, circCDK14 (originating from the yak's CDK14 gene), was identified by sequencing and RNase R treatment. In our previous study, we successfully established a ceRNA network map and identified miR-4492-z, which interacts with circCDK14. Furthermore, using methylation prediction software, we predicted two genes, SRSF3 and hnRNP A1, that have a strong binding relationship with circCDK14; existing research has confirmed their close association with m6A methylation modifications. On the basis of these findings, we comprehensively evaluated the effects of circCDK14, miR-4492-z, SRSF3 and hnRNP A1 on the proliferation and differentiation of yak intramuscular pre-adipocytes using EdU, CCK-8, BODIPY, Oil Red O and qRT-PCR analyses. Mechanistically, the interaction between circCDK14 and miR-4492-z was validated using a dual-luciferase reporter gene assay and rescue experiments. RIP assays revealed the binding interaction of circCDK14 with SRSF3 and hnRNP A1. The MeRIP experiments showed modification of circCDK14 methylation, with SRSF3 and hnRNP A1 promoting the methylation and translocation of circCDK14 from the nucleus to the cytoplasm. In summary, our results suggest that m6A-modified circCDK14 plays a crucial role as an miR-4492-z sponge in regulating IMF deposition in yaks and that the nuclear export of circCDK14 correlates with the expression levels of SRSF3 and hnRNP A1. This study provides a theoretical basis for the improvement of yak meat quality and promotes the development of molecular yak breeding.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"26"},"PeriodicalIF":9.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA-PKcs, a player winding and dancing with RNA metabolism and diseases.","authors":"Jiabao Hou, Mingjun Lu, Jingwei Guo, Jinghong Wu, Chenyang Wang, Ping-Kun Zhou, Teng Ma","doi":"10.1186/s11658-025-00703-z","DOIUrl":"10.1186/s11658-025-00703-z","url":null,"abstract":"<p><p>The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a key kinase in the DNA repair process that responds to DNA damage caused by various factors and maintains genomic stability. However, DNA-PKcs is overexpressed in some solid tumors and is frequently associated with poor prognosis. DNA-PKcs was initially identified as a part of the transcription complex. In recent years, many studies have focused on its nonclassical functions, including transcriptional regulation, metabolism, innate immunity, and inflammatory response. Given the pleiotropic roles of DNA-PKcs in tumors, pharmacological inhibition of DNA-PK can exert antitumor effects and may serve as a potential target for tumor therapy in the future. This review summarizes several aspects of DNA-PKcs regulation of RNA metabolism, including its impact on transcriptional machinery, alternative splicing, and interaction with noncoding RNAs, and provides insights into DNA-PKcs beyond its DNA damage repair function.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"25"},"PeriodicalIF":9.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KLF5 enhances CXCL12 transcription in adipose-derived stem cells to promote endothelial progenitor cells neovascularization and accelerate diabetic wound healing.","authors":"Yunjia Xie, Xuejun Ni, Xiaofen Wan, Nating Xu, Lu Chen, Chensheng Lin, Xi Zheng, Beichen Cai, Qian Lin, Ruonan Ke, Tao Huang, Xuefeng Hu, Biao Wang, Xiuying Shan","doi":"10.1186/s11658-025-00702-0","DOIUrl":"10.1186/s11658-025-00702-0","url":null,"abstract":"<p><strong>Background: </strong>Adipose-derived stem cells (ADSCs) have been shown to accelerate diabetic wound healing by promoting neovascularization, though the underlying mechanisms are not fully understood. This study aims to explore whether ADSCs influence endothelial progenitor cells (EPCs) function to enhance diabetic wound healing.</p><p><strong>Methods: </strong>Human adipose-derived stem cells (hADSCs) were isolated from patient adipose tissue and cultured under normal and high glucose (HG) conditions. RNA sequencing analyzed gene expression, while immunofluorescence validated findings in patient wound tissues. Mouse adipose-derived stem cells (ADSCs) from C57BL/6 mice were evaluated in vitro for their effects on EPCs under HG using EdU, Transwell, and tube formation assays. A diabetic mouse wound model was used to assess ADSCs therapeutic effects via digital imaging, histology, and immunofluorescence. Kruppel-like factor 5 (KLF5), identified via the JASPAR database, was confirmed by immunohistochemistry and immunofluorescence. KLF5 and C-X-C motif chemokine 12 (CXCL12) expression levels were measured by enzyme-linked immunosorbent assay (ELISA), western blot, and quantitative reverse transcription polymerase chain reaction (RT-qPCR), and their relationship was validated through dual-luciferase assays.</p><p><strong>Results: </strong>We constructed a neovascularization-related signature (NRS) comprising 75 genes on the basis of differentially expressed genes (DEGs) linked to neovascularization. GO and KEGG analyses revealed that the NRS is primarily involved in vasculature development and receptor-ligand activity. Seven hub genes (CD34, CXCL12, FGF7, FGF18, FGF1, TEK, KIT) were identified and validated. In a diabetic mouse model, CXCL12 knockdown in ADSCs reduced their ability of promoting wound healing and neovascularization. KLF5 expression was lower in patients with diabetic ulcers and diabetic mice wound tissues compared with normal tissues, while ADSCs treatment significantly increased KLF5 expression in diabetic mice wounds. Dual-luciferase reporter assays confirmed KLF5 as an upstream transcription factor of CXCL12. Additionally, knocking down KLF5 in ADSCs impaired their therapeutic effects on diabetic wound healing. In vitro, the addition of exogenous CXCL12 recombinant protein restored EPCs proliferation, migration, and vasculogenic capacity in a high glucose environment after KLF5 silencing in ADSCs.</p><p><strong>Conclusions: </strong>Our findings underscore the pivotal role of KLF5 in enhancing CXCL12 transcription within ADSCs, thereby facilitating EPC-mediated neovascularization and improving diabetic wound healing. Additionally, KLF5 emerges as a promising therapeutic target for accelerating tissue repair in diabetic wounds.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"24"},"PeriodicalIF":9.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulating chemoresistance and cancer stemness: the CDH17-YAP pathway in distinct cellular states of lung cancer CTC clusters.","authors":"Zujun Que, Dan Qi, Yun Yang, Wang Yao, Jiajun Liu, Yan Li, Yuanyuan Yu, Luyao Wang, Fangfei Li, Ge Zhang, Erxi Wu, Jianhui Tian","doi":"10.1186/s11658-025-00696-9","DOIUrl":"10.1186/s11658-025-00696-9","url":null,"abstract":"<p><strong>Background: </strong>Drug resistance in metastatic lung cancer significantly contributes to patient mortality. This study explores the role of circulating tumor cells (CTCs), the precursors to metastasis, in driving this resistance. We aim to delineate the unique biological traits of CTC clusters in lung cancer and elucidate the mechanisms underlying their resistance to chemotherapy.</p><p><strong>Methods: </strong>We used an ultralow adsorption plate to establish a CTC suspension culture system. Comparisons between adherent and suspension cultures of CTC-TJH-01 cells were made via Cell Counting Kit-8 (CCK-8), western blot, immunofluorescence, and flow cytometry assays to evaluate cell proliferation, drug resistance, and cancer stemness. The tumorigenicity, tumor growth rate, and drug resistance of the CTC clusters were assessed in nude mice. Transcriptomic and proteomic analyses were subsequently conducted to identify differentially expressed genes and proteins in CTC-TJH-01 cells cultured under adherent and suspension conditions. CDH17 gene knockdown in CTC-TJH-01 cells was achieved through RNA interference, and hematoxylin and eosin (HE) staining, immunohistochemistry, and immunofluorescence assays were used to examine the pathological status of these cells.</p><p><strong>Results: </strong>CTC-TJH-01 cells in suspension formed cell clusters and exhibited decreased proliferation, tumorigenicity, and tumor growth, but increased cancer stemness and drug resistance. CDH17 protein expression was significantly upregulated in these clusters, activating the YAP/TAZ pathway. Knocking down CDH17 not only inactivated this pathway but also significantly increased cell proliferation activity and cisplatin sensitivity in CTC-TJH-01 clusters. Additionally, the tumor growth rate was correlated with cisplatin sensitivity. CDH17 knockdown notably promoted the growth of CTC-TJH-01 xenografts and enhanced their sensitivity to cisplatin, although no significant difference was observed compared with those in the control group.</p><p><strong>Conclusions: </strong>The results indicate that lung CTC clusters with stem cell-like properties exhibit chemoresistance, which is linked to an activated CDH17-YAP pathway. Additionally, the effectiveness of cisplatin is primarily observed in tumors with relatively high growth rates, highlighting the connection between tumor growth and sensitivity to chemotherapy.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"23"},"PeriodicalIF":9.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}