Experimental cell research最新文献

{"title":"Downregulation of CTRP1 reduces radio-resistance in glioblastoma cells by inhibiting the expression of CD133 after X-ray and carbon ion irradiation","authors":"Ke Huang ,&nbsp;Luyao Wu ,&nbsp;Dan Xu ,&nbsp;Hong Zhang ,&nbsp;Qiang Liu ,&nbsp;Yi Xie","doi":"10.1016/j.yexcr.2024.114292","DOIUrl":"10.1016/j.yexcr.2024.114292","url":null,"abstract":"<div><div>Glioblastomas (GBMs), the most prevalent primary malignant brain tumors, present significant challenges due to their invasive nature, high recurrence rates, and limited treatment options. Radiotherapy is a cornerstone in the management of GBMs; however, resistance to treatment poses a substantial obstacle. This study investigates the role of adipokine C1q/TNF-related protein 1 (CTRP1) in the radio-sensitivity of GBMs, utilizing both X-ray and carbon ion irradiation. Expression analyses revealed elevated CTRP1 and CD133 levels in GBMs tissues, which were associated with poor patient survival. Carbon ion irradiation demonstrated superior growth inhibition compared to X-ray, particularly in U87 (high CD133) cells. Moreover, CTRP1 expression increased following radiation exposure, especially after X-ray treatment. Knockdown of CTRP1 enhanced radio-sensitivity by reducing cell proliferation and increasing apoptosis, while exacerbating oxidative stress. Bioinformatics analysis revealed CTRP1's involvement in DNA damage repair pathways. Our findings establish a novel connection between CTRP1 and cellular radio-sensitivity. Targeting CTRP1, especially in U87 (high CD133) cells, enhances GBMs radio-sensitivity, offering potential therapeutic avenues.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114292"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"lncRNA-NEF regulates hepatic stellate cells proliferation, cell cycle, apoptosis and ECM synthesis through the ERK1/2/c-Fos axis","authors":"Gang-gang Jia ,&nbsp;Li-xia Lu ,&nbsp;Bin- Li ,&nbsp;Chu-yi Li ,&nbsp;Ying- Zheng ,&nbsp;Jiu-cong Zhang ,&nbsp;Yu-jing He ,&nbsp;Xu-Shi ,&nbsp;Xiao-hui Yu","doi":"10.1016/j.yexcr.2024.114361","DOIUrl":"10.1016/j.yexcr.2024.114361","url":null,"abstract":"<div><div>In this study, we investigated the role of lncRNA-NEF in modulating hepatic stellate cell (HSC) activation, a key process in liver fibrosis. Using the GSE78160 dataset, we identified lncRNA-NEF as downregulated in liver cirrhosis patients. Gene Ontology and KEGG analyses implicated it in transcriptional regulation and cell cycle control. We established an activated HSC model with TGF-β1-treated LX-2 cells and employed RT-qPCR and Western blot to assess lncRNA-NEF and ERK1/2 expression. Lentiviral transfection was used to overexpress lncRNA-NEF in activated LX-2 cells, and its effects on proliferation, apoptosis, and cell cycle were evaluated using EdU staining, CCK-8, Annexin-V PE/7-AAD, TUNEL, and PI-FACS analysis. Overexpression of lncRNA-NEF led to reduced cell proliferation, increased apoptosis, and cell cycle arrest at the S and G2/M phases. We also observed a decrease in ERK1/2, c-Fos, Collagen I, α-SMA, and Bcl-2 expression, and an increase in Caspase-3 expression, as confirmed by Western blot. These results suggest that lncRNA-NEF regulates HSC activation via the ERK1/2/c-Fos axis, potentially offering a therapeutic target for antifibrotic drug development. Our findings provide a molecular basis for understanding the role of lncRNAs in liver fibrosis and highlight the potential of lncRNA-NEF as a novel antifibrotic target.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114361"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tripartite motif (TRIM) proteins roles in the regulation of immune system responses: Focus on autoimmune diseases","authors":"Subasini Uthirapathy ,&nbsp;Abdulrahman T. Ahmed ,&nbsp;Mahmood Jawad ,&nbsp;Vicky Jain ,&nbsp;Suhas Ballal ,&nbsp;Hussein Riyadh Abdul Kareem Al-Hetty ,&nbsp;Gaurav Khandelwal ,&nbsp;Renu Arya ,&nbsp;Muthena kariem ,&nbsp;Yasser Fakri Mustafa","doi":"10.1016/j.yexcr.2024.114379","DOIUrl":"10.1016/j.yexcr.2024.114379","url":null,"abstract":"<div><div>The tripartite motif (TRIM) proteins are well-studied as essential modulators of many processes, including the modulation of several pathways linked to immunological reactions. Most TRIM family members can polyubiquitinate the targeted proteins by acting as E3 ubiquitin ligases. According to current research, TRIMs play a critical role in innate immune response via modifying transcription factors, pattern recognition receptors (PRRs), and key adaptor proteins within innate immunity. It is becoming clearer that TRIMs play important roles in adaptive immune response, especially in the stimulation and promotion of T cells. We highlight the E3 ubiquitin ligase functions of TRIMs in the PRRs axis linked to autoimmune disorders. By focusing on TRIM family members, we also clarify the new approaches to regulating immunological reactions to alleviate autoimmunity.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114379"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced elastin in multiple myeloma niche promotes cell proliferation","authors":"Mozayan Zoabi ,&nbsp;Elina Orbuch ,&nbsp;Oded Komemi ,&nbsp;Osnat Jarchowsky-Dolberg ,&nbsp;Yaron Shraga Brin ,&nbsp;Shelly Tartakover-Matalon ,&nbsp;Metsada Pasmanik-Chor ,&nbsp;Michael Lishner ,&nbsp;Liat Drucker","doi":"10.1016/j.yexcr.2024.114395","DOIUrl":"10.1016/j.yexcr.2024.114395","url":null,"abstract":"<div><div>Multiple myeloma (MM) malignant plasma cells accumulate in the bone marrow (BM) where their interactions with the microenvironment promote disease progression and drug resistance. Previously, we have shown that bone marrow mesenchymal stem cells (BM-MSCs) (MM and normal donors- ND) derived extracellular matrix (ECM) affected MM cell lines differentially with a pro-MM effect attributed to MM-MSCs' ECM. Here we studied the composition of BM-MSC's ECM (ND versus MM) with focus on elastin (ELN). Isolated BM-MSCs' ECM mass spectrometry (proteomics) demonstrated distinct differences in proteins repertoire in a source dependent manner (MM or ND-MSCs) with ELN being the most significantly decreased protein in MM-MSCs ECM. To study this observation, we cultured MM cell lines (MM1S, RPMI-8226) and BM-MSCs with/without ELN and assayed the cells' phenotype. We demonstrated that supplementing ELN to MM cell lines reduced live cell counts and increased cell adhesion. ELN also decreased MM-MSCs' proliferation but did not affect ND-MSCs. Importantly, ELN addition to MM-MSC ECM abrogated its pro-MM effect on MM cells' proliferation. These novel findings underscore a suppressive role for ELN in MM and suggest it may hold potential diagnostic and therapeutic purposes.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114395"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALKBH5 promotes T-cell acute lymphoblastic leukemia growth via m6A-guided epigenetic inhibition of miR-20a-5p","authors":"Jiazhuo Liu ,&nbsp;Xin Zhang ,&nbsp;Yi Liao ,&nbsp;Chunlan Zhang ,&nbsp;Leiwen Peng","doi":"10.1016/j.yexcr.2024.114293","DOIUrl":"10.1016/j.yexcr.2024.114293","url":null,"abstract":"<div><div>This study investigates the role of ALKBH5-mediated m⁶A demethylation in T-cell acute lymphoblastic leukemia (T-ALL). T-ALL cell lines (HPB-ALL, MOLT4, Jurkat, CCRF-CEM) and human T cells were analyzed. CCRF-CEM and Jurkat cells were transfected with si-ALKBH5, miR-20a-5p-inhibitor, and pcDNA3.1-DDX5. The expression levels of <em>ALKBH5</em>, <em>miR-20a-5p</em>, and <em>DDX5</em> in these cells were determined using qRT-PCR and Western blotting. Cell viability, proliferation, colony formation, and apoptosis were assessed using CCK-8, EdU staining, colony formation assay, and flow cytometry. mRNA m6A levels were quantified with an m6A RNA methylation detection reagent, and RNA immunoprecipitation was employed to measure the enrichment of DGCR8 and m6A on the primary transcript <em>pri-miR-20a</em> of <em>miR-20a-5p</em>. Dual-luciferase assay confirmed the binding relationship between <em>miR-20a-5p</em> and <em>DDX5</em>. Results showed that <em>ALKBH5</em> and <em>DDX5</em> were upregulated in T-ALL tissues and cells, whereas <em>miR-20a-5p</em> was downregulated. Silencing <em>ALKBH5</em> inhibited T-ALL cell viability, colony formation, and proliferation, while promoting apoptosis. These effects were reversed by <em>miR-20a-5p</em> inhibition or <em>DDX5</em> overexpression. ALKBH5 reduced the relative m⁶A level in T-ALL cells and decreased <em>miR-20a-5p</em> expression by reducing DGCR8 binding to <em>pri-miR-20a-5p. miR-20a-5p</em> suppressed <em>DDX5</em> transcription. In conclusion, ALKBH5-mediated m⁶A demethylation decreases DGCR8 binding to <em>pri-miR-20a</em>, thereby repressing <em>miR-20a-5p</em> expression and enhancing <em>DDX5</em> expression, ultimately inhibiting T-ALL cell apoptosis and promoting proliferation.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114293"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiling the extracellular vesicles of two human placenta-derived mesenchymal stromal cell populations","authors":"Ramin Khanabdali ,&nbsp;Mozhgan Shojaee ,&nbsp;Jancy Johnson ,&nbsp;Sam Q.K. Law ,&nbsp;Melissa B.L. Lim ,&nbsp;Patrick F. James ,&nbsp;Angus Tester ,&nbsp;Bill Kalionis","doi":"10.1016/j.yexcr.2024.114387","DOIUrl":"10.1016/j.yexcr.2024.114387","url":null,"abstract":"<div><div>Increasing evidence shows extracellular vesicles (EVs) are primarily responsible for the beneficial effects of cell-based therapies. EVs derived from mesenchymal stromal cells (MSCs) show promise as a source of EVs for cell-free therapies. The human placental fetal–maternal interface is a rich and abundant source of MSCs from which EVs can be isolated. This study focusses on chorionic MSCs (CMSC) located on the fetal aspect of the interface and decidual MSCs (DMSC) on the maternal aspect. This study used Ligand-based Exosome Affinity Purification (LEAP) chromatography to isolate EVs from well-characterized placental hTERT-transduced CMSC29 and DMSC23 cell lines, which retain many important stem cell-like properties of primary CMSC and DMSC, respectively. After initial biophysical characterization of the EVs isolated from each cell line, the biological activities and the protein, lipid and small RNA contents of CMSC29-EVs and DMSC23-EVs were compared and assessed.</div><div>LEAP-purified EVs from both sources were validated at the biophysical level by Spectradyne, Cryo-Transmission Electron Microscopy (Cryo-TEM), and Western blot analysis. EVs from each type were labelled with the live cell stain PKH26 and their <em>in vitro</em> uptake and internalization by human dermal fibroblast cells was assessed, as well as their phosphorylation of the protein kinase B/AKT (AKT) pathway. The protein and lipid contents were analyzed by mass spectrometry and the nucleic acid content by RNA sequencing (RNA-seq). Lastly, the biological activities of the EVs were evaluated in a BioMAP® Diversity PLUS® screen system across a panel of 12 human primary cell-based systems and <em>in vitro</em> cell proliferation.</div><div>EVs isolated from both DMSC23 and CMSC29 significantly increased proliferation of fibroblasts and showed phosphorylation of the AKT pathway. Protein mass spectrometry analysis identified a large number of proteins including cell surface receptors, cytokines, chemokines, matrix molecules and enzymes in both EV types. Lipidomic analysis identified species including phosphatidylcholine, triacylglycerides and diacylglycerides in both DMSC23 and CMSC29-derived EVs. There were some significant differences in identified microRNAs (miRNAs) between the two EV types. The top differentially expressed miRNAs between the two EV types show pathways association with matrix interaction, transcriptional regulation, proliferation, cellular protein modification processes, and vasculogenesis. Differences were also detected between DMSC23- and CMSC29-EVs in the biological activity they displayed in the BioMAP® Diversity PLUS® screen.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114387"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ganoderma lucidum extract reverses multidrug resistance in breast cancer cells through inhibiting ATPase activity of the P-glycoprotein via MAPK/ERK signaling pathway","authors":"Chunwei Jiao ,&nbsp;Jinshou Qiu ,&nbsp;Congcong Gong ,&nbsp;Xiaoyi Li ,&nbsp;Huijia Liang ,&nbsp;Chunyan He ,&nbsp;Sien Cen ,&nbsp;Yizhen Xie","doi":"10.1016/j.yexcr.2024.114355","DOIUrl":"10.1016/j.yexcr.2024.114355","url":null,"abstract":"<div><div>Breast cancer represents a persistent global health challenge, with multidrug resistance (MDR) posing a significant obstacle to effective treatment. In this study, we investigate the potential of <em>Ganoderma lucidum</em> extract (GLE) in reversing MDR in breast cancer and delve into the underlying mechanisms. We establish a robust in vitro 3D model of breast cancer with acquired MDR induced by paclitaxel. Utilizing the CCK-8 method, we assess the impact of GLE on cytotoxic drug sensitivity to determine its in vitro MDR reversal activity.</div><div>Our results reveal that GLE enhances the toxicity of paclitaxel in breast cancer cells by inhibiting the ATPase activity of P-glycoprotein (P-gp) and increasing the intracellular and extracellular excretion of P-gp substrates, all without significantly altering P-gp protein expression. Additionally, GLE inhibits the phosphorylation of ERK1/2, suggesting that the enhanced sensitivity of breast cancer cells to paclitaxel by GLE is associated with the MAPK pathway. These findings indicate that GLE may inhibit P-gp-mediated drug efflux via the MAPK pathway, thus effectively overcoming paclitaxel resistance in breast cancer.</div><div>This study provides valuable insights into the potential clinical applications of GLE in reversing multidrug resistance, offering hope for improved breast cancer treatment strategies.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114355"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The anillin knockdown in the Drosophila nervous system shows locomotor and learning defects","authors":"Man Anh Huynh ,&nbsp;Dang Thi Phuong Thao ,&nbsp;Hideki Yoshida","doi":"10.1016/j.yexcr.2024.114364","DOIUrl":"10.1016/j.yexcr.2024.114364","url":null,"abstract":"<div><div>Anillin (Ani) is an evolutionarily conserved protein with a multi-domain structure that cross-links cytoskeletal proteins and plays an essential role in the formation of the contractile ring during cytokinesis. However, Ani is highly expressed in the human central nervous system (CNS), and it scaffolds myelin in the CNS of mice and modulates neuronal migration and growth in <em>Caenorhabditis elegans</em>. Although Ani is also highly expressed in the <em>Drosophila</em> CNS, its role remains unclear. In the present study, we showed that Ani is not only highly expressed in larval neuroblasts of the CNS, but also weakly expressed in the neuromuscular junction (NMJ) and axons. In addition, the <em>ani</em> knockdown in the nervous system led to pupal lethality, larval locomotor defects, and learning disability, along with abnormal morphology of the NMJ and distribution patterns of the mature neuropil in the CNS. These results show that Ani plays an important role also in the <em>Drosophila</em> nervous system.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114364"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small RNA sequencing of differentiated astrocytoma exposed to NMOSD patient sera reveals perturbations in neurodegenerative signaling","authors":"Pallavi Chatterjee ,&nbsp;Shouvik Chakravarty ,&nbsp;Nidhan K. Biswas ,&nbsp;Santosh Trivedi ,&nbsp;Ashis Datta ,&nbsp;Debashis Mukhopadhyay","doi":"10.1016/j.yexcr.2024.114375","DOIUrl":"10.1016/j.yexcr.2024.114375","url":null,"abstract":"<div><div>The signaling pathways behind severe astrocytic lysis with Aquaporin4 auto-antibody (AQP4-IgG) seropositivity, and reactive astrocytosis with myelin oligodendrocyte glycoprotein auto-antibody (MOG-IgG) seropositivity, remain largely unexplored in Neuromyelitis optica spectrum disorder (NMOSD), while almost no molecular details being known about double-seronegative (DN) patients. Recent discovery of glial fibrillary acidic protein (GFAP) in DN NMOSD patients’ cerebrospinal fluid, akin to AQP4-IgG + ve cases, suggests astrocytopathy. Here, we aim to study small non coding RNA (sncRNA) signature alterations in astrocytes exposed to AQP4-IgG + ve and MOG-IgG + ve patient sera, and their potential resemblance with DN-NMOSD. Next Generation Sequencing (NGS) revealed differential expression of several microRNAs with notable alterations in hsa-miR-6824-3p, hsa-miR-324-5p and hsa-miR-4466 respectively upon sera treatment. Results with DN-NMOSD patient sera are majorly similar to that of AQP4+ve sera. Strikingly, in all three treatments, hsa-miR-200b-3p was significantly upregulated. Functional enrichment analysis revealed that Hippo and FoxO signaling pathways were primarily impacted in AQP4-IgG + ve and double negative sera treated cells whereas, MOG-IgG + ve sera treatment perturbed the PI3K-Akt and MAPK signaling pathways. Furthermore, NGS also revealed differential expression of several piRNAs in cells upon treatment with AQP4-IgG + ve and MOG-IgG + ve sera and VEGF signaling was identified as the common target of differentially expressed piRNAs of both the groups. This study, for the first time, revealed that the molecular pathophysiology of double-seronegative NMOSD might involve astrocytopathy akin to AQP4+ve NMOSD, thus pointing towards the possible existence of unidentified astrocytic autoimmune targets and identified the major alterations in intracellular sncRNAs and the associated overall cellular signaling pathways that potentially contribute to the fate of astrocytes during the progression of the disease.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114375"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of THBS1 axis contributes to the antitumor effect of PA-MSHA in anaplastic thyroid cancer","authors":"Zhe Li ,&nbsp;Ting He ,&nbsp;Zhichao Xing ,&nbsp;Jingqiang Zhu ,&nbsp;Wenshuang Wu ,&nbsp;Anping Su","doi":"10.1016/j.yexcr.2024.114373","DOIUrl":"10.1016/j.yexcr.2024.114373","url":null,"abstract":"<div><div>Anaplastic thyroid cancer (ATC) is the most aggressive form of thyroid cancer, has the worst prognosis, and lacks effective treatment in clinical practice. Thrombospondin-1 (THBS1) is a multifunctional extracellular matrix (ECM) glycoprotein that regulates cell proliferation, apoptosis, and metastasis, and is considered a potential clinical biomarker for the monitoring and prognostication of various tumors. However, the specific roles and molecular mechanisms of action of THBS1 in ATC remain unclear. In this study, we found that Pseudomonas aeruginosa-mannose sensitive hemagglutinin (PA-MSHA), a THBS1 inhibitor, significantly inhibited ATC tumor growth both <em>in vitro</em> and <em>in vivo</em>. Mechanistically, we demonstrated that <em>THBS1</em> was the target gene of PA-MSHA in ATC and identified the THBS1/FAK/AKT axis as the key antitumor signaling pathway. Furthermore, we confirmed that THBS1 was overexpressed in ATC tumors and that high levels of THBS1 were associated with a poorer prognosis in thyroid cancer. Silencing <em>THBS1</em> significantly decreased p-FAK and p-AKT levels, resulting in significant inhibition of cell proliferation and apoptosis in ATC cells. These findings suggest that the THBS1/FAK/AKT axis is a promising therapeutic target for ATC treatment.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114373"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}