JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"RETRACTION: Chemosensitization in Non-small Cell Lung Cancer Cells by IKK Inhibitor Occurs via NF-κB and Mitochondrial Cytochrome C Cascade","authors":"","doi":"10.1111/jcmm.70160","DOIUrl":"10.1111/jcmm.70160","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <p><b>RETRACTION</b>: X. Jin, L. Qiu, D. Zhang, M. Zhang, Z. Wang, Z. Guo, C. Deng, and C. Guo, “Chemosensitization in Non-small Cell Lung Cancer Cells by IKK Inhibitor Occurs via NF-κB and Mitochondrial Cytochrome C Cascade,” <i>Journal of Cellular and Molecular Medicine</i> 13, no. 11–12 (2009): 4596–4607, https://doi.org/10.1111/j.1582-4934.2008.00601.x.</p>\u0000 \u0000 <p>The above article, published online on 4 March 2010 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Stefan N. Constantinescu; the Foundation for Cellular and Molecular Medicine; and John Wiley &amp; Sons Ltd.</p>\u0000 \u0000 <p>The retraction has been agreed due to concerns raised by third parties on the data presented in the article. Specifically, image elements in Figures 2A and 6 were found to have been previously published by the same author group in a different scientific context. Further investigation by the publisher uncovered that the same concerns affected additional image elements in Figures 3B, 3C and 7A. The corresponding author was unresponsive to requests for clarification. For these reasons, the article is retracted as its conclusions are deemed invalid by the editors. Confirmation of retraction could not be obtained by the remaining co-authors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466365","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":"RETRACTION: Twist1 Accelerates Tumour Vasculogenic Mimicry by Inhibiting Claudin15 Expression in Triple-Negative Breast Cancer","authors":"","doi":"10.1111/jcmm.70162","DOIUrl":"10.1111/jcmm.70162","url":null,"abstract":"<p><b>RETRACTION</b>: D. Zhang, B. Sun, X. Zhao, H. Sun, J. An, X. Lin, D. Zhu, X. Zhao, X. Wang, F. Liu, Y. Zhang, J. Liu, Q. Gu, X. Dong, Z. Qiu, Z. Liu, H. Qi, N. Che, J. Li, R. Cheng and X. Zheng, “Twist1 Accelerates Tumour Vasculogenic Mimicry by Inhibiting Claudin15 Expression in Triple-negative Breast Cancer,” <i>Journal of Cellular and Molecular Medicine</i> 24, no. 13 (2020): 7163–7174, https://doi.org/10.1111/jcmm.15167.</p><p>The above article, published online on 29 May 2020 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; journal Editor-in-Chief, Stefan N. Constantinescu; the Foundation for Cellular and Molecular Medicine; and John Wiley &amp; Sons Ltd. The retraction has been agreed as two images presented in figure 3b were found to be duplicated in figure 4b, but these images are described as representing different cells or different experimental conditions. Furthermore, a duplication of an image included in Figure 2 was found in a paper published earlier in another journal by some of the same authors. The authors provided some data and an explanation; however, this was not considered satisfactory. Given the extent of the identified issues, the editors have lost confidence in the data presented.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466366","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":"Letter to editor on ‘isolation and characterization of human Wharton's jelly mesenchymal stem cell-derived extracellular vesicles’","authors":"Saravanan Sampoornam Pape Reddy,&nbsp;Delfin Lovelina Francis,&nbsp;Vishal Kulkarni,&nbsp;Sukhbir Singh Chopra","doi":"10.1111/jcmm.70168","DOIUrl":"10.1111/jcmm.70168","url":null,"abstract":"&lt;p&gt;We have carefully reviewed the methodology described in the study titled ‘Isolation and Characterization of Human Wharton's Jelly Mesenchymal Stem Cell-Derived Extracellular Vesicles’ by Torabi et al.,&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; published in the &lt;i&gt;Journal of Cellular and Molecular Medicine&lt;/i&gt;. This letter concerns the isolation, characterization, and functional assessment of extracellular vesicles (EVs) derived from Wharton's Jelly mesenchymal stem cells (WJ-MSCs) and their effects on macrophages and stellate cells. While the study presents a comprehensive framework, there are several methodological concerns that warrant further clarification or may pose potential conflicts regarding the robustness and reproducibility of the results. Although the authors provide a comprehensive overview of the isolation and characterization WJ-MSC derived EVs, the experimental design and interpretation of the data merit further scrutiny.&lt;/p&gt;&lt;p&gt;The authors detail a multistep ultracentrifugation process to isolate EVs, with the final fractions labelled as EV20K and EV110K. However, the reported methods lack adequate controls to confirm the purity of these EV populations. Specifically, there is no mention of assessing the presence of other potential contaminants, such as protein aggregates or apoptotic bodies, which could confound the results. The absence of additional characterization techniques, such as nanoparticle tracking analysis (NTA) or density gradient purification raises concerns about the reliability of the size distribution data obtained via dynamic light scattering (DLS). Furthermore, a more stringent debris removal step, such as a lower-speed centrifugation or filtration, would enhance the purity of the isolated EV populations.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Given that EV populations differ greatly in size and content, the omission of such steps could influence the downstream biological assays, particularly when assessing functional outcomes.&lt;/p&gt;&lt;p&gt;The authors utilized flow cytometry to measure the uptake of calcein-labelled EVs by UCB-derived monocytes. However, the experimental conditions surrounding the labelling and washing steps may inadvertently affect the quantification of EV uptake. It is critical that the authors provide a more detailed methodology regarding how they ensured the complete removal of unbound calcein dye and how this might affect the interpretation of their flow cytometry results. Although Western blotting for EV markers (CD63, CD81) and the absence of calnexin were performed to validate EV identity, it would be beneficial to include NTA in addition to DLS for more accurate size distribution and concentration profiling. The use of calcein AM to label EVs for the uptake study introduces potential issues; calcein dye can leak from vesicles and be taken up by cells, which may inflate the reported uptake rates. A more vesicle-specific dye (such as DiD or PKH dyes) could reduce this confounding factor, providing a clearer understanding o","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501104","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":"Dendritic cell-derived lncRNAs in patients with acute coronary syndrome","authors":"Zhenglong Wang,&nbsp;K. E. Changhao,&nbsp;Yuheng Chen,&nbsp;Yongchao Zhao,&nbsp;Yuanjie He,&nbsp;Xiao Liang,&nbsp;Qingxian Tu,&nbsp;Min Xu,&nbsp;Fujia Guo,&nbsp;Junbo Ge,&nbsp;Bei Shi","doi":"10.1111/jcmm.70057","DOIUrl":"10.1111/jcmm.70057","url":null,"abstract":"<p>Long non-coding RNAs (lncRNAs) and dendritic cells (DC) play crucial roles in the development of acute coronary syndrome (ACS); however, the mechanisms remain unclear. To investigate this, we analysed the differentially expressed lncRNAs in monocyte-derived DCs (moDCs) from patients with ACS. Peripheral blood mononuclear cells were transformed into moDCs. Cellular morphology and expression levels of moDC-specific markers (CD80, CD86, CD11c, CD14 and HLA-DR) were analysed using electron microscopy (EM) and flow cytometry (FCM), respectively. Differentially expressed lncRNAs and their functions were predicted using gene sequencing, gene ontology and the Kyoto Encyclopedia of Genes and Genomes. The expression levels of markers, signalling pathway molecules (p-PI3K and p-AKT), inflammatory cytokines (IL-6 and IL-12p70) and target gene (C-C motif chemokine ligand (<i>CCL</i>) 15 and <i>CCL14</i>) were analysed by overexpression or silencing of candidate lncRNAs. EM revealed the cells to be suspended in dendritic pseudopodia. CD11c and HLA-DR were upregulated, while CD80 and CD86 were downregulated. Comparison between the UA versus ST group showed the highest number of differentially expressed lncRNAs (<i>n</i> = 113), followed by UA versus NST (<i>n</i> = 115), CON versus NST (<i>n</i> = 49) and CON versus ST (<i>n</i> = 35); however, the number was low for CON versus UA and ST versus NST groups. moDC-specific marker expression, signalling pathway molecules, inflammatory cytokines and <i>CCL14</i> were upregulated following lentiviral overexpression of smart silencer-<i>CCL15-CCL14</i>; however, expression levels decreased following transfection with siRNA. The morphology, function and lncRNA expression of moDCs differ depending on the type of ACS. The differentially expressed lncRNAs, particularly CCL15-CCL14, regulate the function of moDCs. Thus, our study provides new insights regarding the role of lncRNAs in ACS and indicates the potential use of CCL15-CCL14 as a novel diagnostic marker and therapeutic target.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466359","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":"Hoxc10-mediated ‘positional memory’ regulates cartilage formation subsequent to femoral heterotopic grafting","authors":"Haoyue Song,&nbsp;Yujia Hao,&nbsp;Qingpeng Xie,&nbsp;Xiaohang Chen,&nbsp;Na Li,&nbsp;Jia Wang,&nbsp;Xiaoxuan Zhang,&nbsp;Yuan Zhang,&nbsp;Jinjia Hong,&nbsp;Shuyun Xue,&nbsp;Pengfei Zhang,&nbsp;Si Xie,&nbsp;Xing Wang","doi":"10.1111/jcmm.70140","DOIUrl":"10.1111/jcmm.70140","url":null,"abstract":"<p>The Hox gene plays a crucial role in the bone development, determining their structure and morphology. Limb bone grafts expressing Hox positive genes are commonly used for free transplantation to repair Hox negative mandibular critical bone defects. However, the specific role of original Hox genes in newly formed bone during the cross-layer bone grafting healing process remains unexplored. Our findings demonstrate that femurs ectopically grafted into the mandibular environment retained a significant ability to differentiate into cartilage and form cartilaginous callus, which may be a key factor contributing to differences in bone graft healing. Hoxc10, an embryonic layer-specific genes, regulates cartilage formation during bone healing. Mechanistically, we observed Hoxc10 retention in co-cultured femoral BMSCs. Knocking out Hoxc10 narrows the bone gap and reduces cartilage formation. In summary, we reveal Hoxc10's ‘positional memory’ after adult cross-layer bone graft, influencing the outcomes of autologous bone graft.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466362","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":"Role of KLF4 and SIAT7A interaction accelerates myocardial hypertrophy induced by Ang II","authors":"Qiying Yao,&nbsp;Xinrui Hu,&nbsp;Tiantian Bian,&nbsp;Qing Zhang,&nbsp;Zhao Xue,&nbsp;Yuesheng Lv,&nbsp;Shupeng Ren,&nbsp;Yue Chen,&nbsp;Dongmei Zhang,&nbsp;Liang Chen","doi":"10.1111/jcmm.70144","DOIUrl":"10.1111/jcmm.70144","url":null,"abstract":"<p>Sialylation catalysed by sialyltransferase 7A (SIAT7A) plays a role in the development of cardiac hypertrophy. However, the regulatory mechanisms upstream of SIAT7A in this context remain poorly elucidated. Previous study demonstrated that KLF4 activates the <i>SIAT7A</i> gene in ischemic myocardium by binding to its promoter region. Nevertheless, the potential involvement of KLF4 in regulating SIAT7A expression in Ang II-induced hypertrophic cardiomyocytes remains uncertain. This study seeks to deepen the underlying mechanisms of the KLF4 and SIAT7A interaction in the progression of Ang II-induced cardiac hypertrophy. The results showed a concurrent increase in SIAT7A and KLF4 levels in hypertrophic myocardium of essential hypertension patients and in hypertrophic cardiomyocytes stimulated by Ang II. In vitro experiments revealed that reducing KLF4 levels led to a decrease in both SIAT7A synthesis and Sialyl-Tn antigen expression, consequently inhibiting Ang II-induced cardiomyocyte hypertrophy. Intriguingly, reducing SIAT7A levels also resulted in decreased KLF4 expression and suppression cardiomyocyte hypertrophy. Consistent with this, elevating SIAT7A levels increased KLF4 expression and exacerbated cardiomyocyte hypertrophy in both in vivo and in vitro experiments. Additionally, a time-course analysis indicated that KLF4 expression preceded that of SIAT7A. Luciferase reporter assays further confirmed that modulating <i>SIAT7A</i> levels directly influenced the transcriptional activity of <i>KLF4</i> in cardiomyocytes. In summary, KLF4 expression is upregulated in cardiomyocytes treated with Ang II, which subsequently induces the expression of SIAT7A. The elevated levels of SIAT7A, in turn, enhance the transcription of <i>KLF4</i>. These findings suggest a positive feedback loop between KLF4 and SIAT7A-Sialyl-Tn, ultimately promoting Ang II-induced cardiac hypertrophy.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466367","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":"Single-cell and spatial transcriptomics reveal apelin/APJ pathway's role in microvessel formation and tumour progression in hepatocellular carcinoma","authors":"Yongfu Zhu,&nbsp;Pengcheng Zhang,&nbsp;Xingxing Huo,&nbsp;Yi Ling,&nbsp;Xiang Lv,&nbsp;Shengyou Lin,&nbsp;Hang Song","doi":"10.1111/jcmm.70152","DOIUrl":"10.1111/jcmm.70152","url":null,"abstract":"<p>The apelin receptor (APJ) is a key player in tumour angiogenesis, but its role in hepatocellular carcinoma (HCC) remains unclear. This study aims to elucidate the function of the apelin/APJ pathway in HCC using a multi-omics approach and identify potential therapeutic biomarkers. Differentially expressed genes related to the apelin/APJ axis were identified from bulk transcriptomics to reveal HCC-associated disparities. Single-cell and spatial transcriptomics were used to localize and analyse the function of these genes. Machine learning models were constructed to predict outcomes based on apelin/APJ expression, and experimental validation was conducted to explore the pathway's impact on HCC angiogenesis. Single cell analysis revealed an overexpression of APJ/Aplin in the endothelium. The stemness of endothelial cell (EC) with high apelin/APJ was enhanced, as well as the expression of TGFb, oxidative stresses and PI3K/AKT pathway genes. Spatial transcriptomics confirmed that EC populations with high APJ scores were enriched within the tumour. Machine learning models showed high prognostic accuracy. High APJ expression was linked to worse outcomes (<i>p</i> = 0.001), and AUC values were high (1 year, 3 year, 5 year) (0.95, 0.97, 0.98). Immune suppression and non-responsiveness of immune therapy were also seen in high-risk groups. The experimental validation showed that silencing apelin reduced angiogenesis (<i>p</i>  &lt; 0.05), endothelial proliferation, decreased expression of ANG2, KLF2, VEGFA and lower ERK1/2 phosphorylation. Apelin may serve as a potential therapeutic target in HCC, given its role in promoting tumour angiogenesis and poor patient outcomes.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466369","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":"Unveiling exosomes: Cutting-edge isolation techniques and their therapeutic potential","authors":"Farnaz Sani,&nbsp;Faezeh Shafiei,&nbsp;Farshad Dehghani,&nbsp;Yasaman Mohammadi,&nbsp;Mohammadhossein Khorraminejad-Shirazi,&nbsp;Abbas Fazel Anvari-Yazdi,&nbsp;Zahra Moayedfard,&nbsp;Negar Azarpira,&nbsp;Mahsa Sani","doi":"10.1111/jcmm.70139","DOIUrl":"10.1111/jcmm.70139","url":null,"abstract":"<p>Exosomes are one type of nanosized membrane vesicles with an endocytic origin. They are secreted by almost all cell types and play diverse functional roles. It is essential for research purposes to differentiate exosomes from microvesicles and isolate them from other components in a fluid sample or cell culture medium. Exosomes are important mediators in cell–cell communication. They deliver their cargos, such as mRNA transcripts, microRNA, lipids, cytosolic and membrane proteins and enzymes, to target cells with or without physical connections between cells. They are highly heterogeneous in size, and their biological functions can vary depending on the cell type, their ability to interact with recipient cells and transport their contents, and the environment in which they are produced. This review summarized the recent progress in exosome isolation and characterization techniques. Moreover, we review the therapeutic approaches, biological functions of exosomes in disease progression, tumour metastasis regulation, immune regulation and some ongoing clinical trials.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466372","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":"HDAC7 promotes ovarian cancer malignancy via AKT/mTOR signalling pathway","authors":"Qi Feng,&nbsp;Sheng Hao,&nbsp;Xiongxiu Liu,&nbsp;Zhong Yan,&nbsp;Kai Sheng,&nbsp;Yanping Li,&nbsp;Peng Zhang,&nbsp;Xiugui Sheng","doi":"10.1111/jcmm.70120","DOIUrl":"10.1111/jcmm.70120","url":null,"abstract":"<p>Ovarian cancer is of the most lethal malignancy and causes serious threat to women health worldwide. A deep understanding of molecular mechanisms underlying ovarian cancer progression is critical for the development of promising therapeutic strategies. In this study, we aimed to employ immunohistochemistry to determine the protein level of HDAC7 in patient tissues, our data showed HDAC7 levels are upregulated in tumour tissues. In addition, we also performed Kaplan–Meier survival analysis to investigate the association between HDAC7 expression and clinical prognosis, and found that HDAC7 expression was associated with poor prognosis in ovarian cancer patients. Inhibition of HDAC7 cells resulted in lower cell proliferation, invasion and colony formation. Furthermore, we also found that HDAC7 inhibition suppressed PI3K/AKT/mTOR pathway. In contrast, exogenous HDAC7 expression activated the PI3K/AKT/mTOR pathway in HDAC7 knockout cells and rescued the cell proliferation, invasion and colony formation. However, inhibition of p-AKT induced lower cell proliferation, metastasis and colony formation abilities. In murine model, HDAC7 KO significantly decreased the tumour burden. These data indicate that HDAC7 is involved in regulation of PI3K/AKT/mTOR pathway and targeting of HDAC7 could be potential therapeutic strategy in the treatment of ovarian cancer.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466361","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":"JAK2V617F-dependent down regulation of SHP-1 expression participates in the selection of myeloproliferative neoplasm cells in the presence of TGF-β","authors":"Céline Aoun,&nbsp;Nabih Maslah,&nbsp;Saravanan Ganesan,&nbsp;Norman Salomao,&nbsp;Romane Gendron,&nbsp;Sarah Awan Toor,&nbsp;Gil Letort,&nbsp;Panhong Gou,&nbsp;Mélina Bonnamy,&nbsp;Véronique Parietti,&nbsp;Jean-Jacques Kiladjian,&nbsp;Stephane Giraudier,&nbsp;Bruno Cassinat","doi":"10.1111/jcmm.70138","DOIUrl":"10.1111/jcmm.70138","url":null,"abstract":"<p>Myeloproliferative neoplasms (MPNs) are characterized by an increased production of blood cells due to the acquisition of mutations such as JAK2^V617F. TGF-β, whose secretion is increased in MPN patients, is known to negatively regulate haematopoietic stem cell (HSC) proliferation. Using an isogenic JAK2^V617F or JAK2 wild-type UT-7 cell line we observed that JAK2^V617F cells resist to TGF-β antiproliferative activity. Although TGF-β receptors and SMAD2/3 expressions are similar in both cell types, TGF-β-induced phosphorylation of SMAD2/3 is reduced in UT-7 JAK2^V617F cells compared with JAK2 WT cells. We confirmed that JAK2^V617F mutated cells are resistant to the antiproliferative effect of TGF-β in a competitive assay as we observed a positive selection of JAK2^V617F cells when exposed to TGF-β. Using cell lines, CD34-positive cells from MPN patients and bone marrow cells from JAK2^V617F knock-in mice we identified a down regulation of the SHP-1 phosphatase, which is required for the regulation of HSC quiescence by TGF-β. The transduction of SHP-1 cDNA (but not a phosphatase inactive cDNA) restores the antiproliferative effect of TGF-β in JAK2^V617F mutated cells. Finally, SC-1, a known agonist of SHP-1, antagonized the selection of JAK2^V617F mutated cells in the presence of TGF-β. In conclusion, we show a JAK2-dependent down regulation of SHP-1 in MPN patients' cells which is related to their resistance to the antiproliferative effect of TGF-β. This may participate in the clonal selection of cancer cells in MPNs.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466364","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}