Neoplasia最新文献

{"title":"Corrigendum to “Androgen receptor degraders overcome common resistance mechanisms developed during prostate cancer treatment” [Neoplasia, Volume 22, Issue 2 (2020) 111–119]","authors":"Steven Kregel , Chao Wang , Xin Han , Lanbo Xiao , Ester Fernandez-Salas , Pushpinder Bawa , Brooke L. McCollum , Kari Wilder-Romans , Ingrid J. Apel , Xuhong Cao , Corey Speers , Shaomeng Wang , Arul M. Chinnaiyan","doi":"10.1016/j.neo.2024.101064","DOIUrl":"10.1016/j.neo.2024.101064","url":null,"abstract":"","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"57 ","pages":"Article 101064"},"PeriodicalIF":4.8,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NEDD9 is transcriptionally regulated by HDAC4 and promotes breast cancer metastasis and macrophage M2 polarization via the FAK/NF-κB signaling pathway","authors":"Wenhong Liu,&nbsp;Guanghua Luo","doi":"10.1016/j.neo.2024.101059","DOIUrl":"10.1016/j.neo.2024.101059","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer is a malignancy with a generally poor prognosis. With the advancement of molecular research, we have gained deeper insights into the cellular processes that drive breast cancer development. However, the precise mechanisms remain elusive.</div></div><div><h3>Results</h3><div>Based on the CPTAC database, we found that NEDD9 expression is up-regulated in breast cancer tissues and is associated with poor prognosis in breast cancer patients. Functional experiments showed that NEDD9 promotes tumor growth and metastasis both in vitro and in vivo. Overexpression of NEDD9 disrupts mammary epithelial acinus formation and triggers epithelial-mesenchymal transition in breast cancer cells, effects that are reversed upon NEDD9 gene silencing. Mechanistically, NEDD9 upregulates its expression by inhibiting HDAC4 activity, leading to enhanced H3K9 acetylation of the NEDD9 gene promoter and activation of the FAK/NF-κB signaling pathway. Furthermore, NEDD9 overexpression promotes IL-6 secretion, which further drives breast cancer progression. Notably, NEDD9 activation fosters the pro-tumoral M2 macrophage polarization in the tumor microenvironment. NEDD9 stimulates IL-6 secretion, polarizes monocytes towards an M2-like phenotype, and enhances BC cell invasiveness.</div></div><div><h3>Conclusions</h3><div>These findings suggest that NEDD9 upregulation plays a pivotal role in breast cancer metastasis and macrophage M2 polarization via the FAK/NF-κB signaling axis. Targeting NEDD9 may offer a promising therapeutic approach for breast cancer treatment.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"57 ","pages":"Article 101059"},"PeriodicalIF":4.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142318426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and genetic profile of Chinese patients with indolent natural killer-cell lymphoproliferative disorder of the gastrointestinal tract","authors":"Hongyun Chen ,&nbsp;Congwei Jia ,&nbsp;Daobin Zhou ,&nbsp;Danqing Zhao ,&nbsp;Yan Zhang ,&nbsp;Hao Cai ,&nbsp;Qiang Wang ,&nbsp;Yueyi Zhang ,&nbsp;Wei Zhang","doi":"10.1016/j.neo.2024.101048","DOIUrl":"10.1016/j.neo.2024.101048","url":null,"abstract":"<div><p>Indolent natural killer cell lymphoproliferative disorder of the gastrointestinal tract (iNKLPD-GI) is an uncommon, recently recognized lymphoid proliferation of mature NK cells primarily manifesting in the GI tract. Unlike NK/T lymphoma, iNKLPD-GI exhibits a rather indolent clinical course, underscoring the need for cautious management to prevent unnecessary interventions. However, clinical and molecular features of this entity have not been thoroughly understood. This study aimed to add more information to the current knowledge of this disease. Seven patients with iNKLPD-GI were included in our study. Clinical data included initial symptoms, endoscopic manifestations, pathological features, and therapies. Besides, next-generation sequencing was arranged to explore the underlying genetic mechanism of this disease. In our study, iNKLPD-GI in the urinary bladder was first identified. Edema of extremities (3, 42.8 %) was the most prevalent onset symptom which was reported for the first time. Pathological and immunohistological features were found to display the phenotype of NK cells. Unlike extranodal NK/T cell lymphoma, Epstein-Barr virus-encoded small RNA (EBER) were negative in all patients. Moreover, we found that two patients harbored <em>JAK3</em> mutation. Apart from <em>JAK</em>3 K563_C565del previously reported in the literature, we discovered new <em>JAK</em>3 mutation sites. Other mutations including <em>BRAF, KRAS</em>, and <em>SH2B3</em> were also identified. In conclusion, iNKLPD-GI was an indolent atypical NK-cell proliferation with diverse clinical characteristics. “Watch and wait” therapy was preferable to intense chemotherapy. Recurrent <em>JAK3</em> mutation may be the underlying mechanism responsible for the neoplastic nature of the disease and may serve as a potential target for patients with severe symptoms.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"57 ","pages":"Article 101048"},"PeriodicalIF":4.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000903/pdfft?md5=655c9e682613ef3b4ee699394f962f2a&pid=1-s2.0-S1476558624000903-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142172092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncolytic adenovirus MEM-288 encoding membrane-stable CD40L and IFNβ induces an anti-tumor immune response in high grade serous ovarian cancer","authors":"Pamela N. Peters ,&nbsp;Regina S. Whitaker ,&nbsp;Felicia Lim ,&nbsp;Shonagh Russell ,&nbsp;Elizabeth A. Bloom ,&nbsp;Justin Pollara ,&nbsp;Kyle C. Strickland ,&nbsp;Mark J. Cantwell ,&nbsp;Amer Beg ,&nbsp;Andrew Berchuck ,&nbsp;Scott Antonia ,&nbsp;Rebecca A. Previs","doi":"10.1016/j.neo.2024.101056","DOIUrl":"10.1016/j.neo.2024.101056","url":null,"abstract":"<div><p>Single agent immune checkpoint inhibitors have been ineffective for patients with advanced stage and recurrent high grade serous ovarian cancer (HGSOC). Using pre-clinical models of HGSOC, we evaluated the anti-tumor and immune stimulatory effects of an oncolytic adenovirus, MEM-288. This conditionally replicative virus encodes a modified membrane stable CD40L and IFNβ. We demonstrated this virus successfully infects HGSOC cell lines and primary human ascites samples <em>in vitro</em>. We evaluated the anti-tumor and immunostimulatory activity <em>in vivo</em> in immune competent mouse models. Intraperitoneal delivery of MEM-288 decreased ascites and solid tumor burden compared to controls, and treatment generated a systemic anti-tumor immune response. The tumor microenvironment had a higher proportion of anti-tumor macrophages and decreased markers of angiogenesis. MEM-288 is a promising immunotherapy agent in HGSOC, with further pre-clinical studies required to understand the mechanism of action in the peritoneal microenvironment and clinical activity in combination with other therapies.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"57 ","pages":"Article 101056"},"PeriodicalIF":4.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000976/pdfft?md5=957f4aa99bbc395267bdcb6a4216417f&pid=1-s2.0-S1476558624000976-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142229456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probing the glioma micro-environment: Analysis using biopsy in combination with ultra-fast cyclic immunolabeling","authors":"Thomas S. van Solinge ,&nbsp;Juhyun Oh ,&nbsp;Erik Abels ,&nbsp;Peter Koch ,&nbsp;Xandra O. Breakefield ,&nbsp;Ralph Weissleder ,&nbsp;Marike L.D. Broekman","doi":"10.1016/j.neo.2024.101051","DOIUrl":"10.1016/j.neo.2024.101051","url":null,"abstract":"<div><p>The interaction between gliomas and the immune system is poorly understood and thus hindering development of effective immunotherapies for glioma patients. The immune response is highly variable during tumor development, and affected by therapies such as surgery, radiation, and chemotherapy. Currently, analysis of these local changes is difficult due to poor accessibility of the tumor and high-morbidity of sampling. In this study, we developed a model for repeat-biopsy in mice to study these local immunological changes over time. Using fine needle biopsy we were able to safely and repeatedly collect cells from intracranial tumors in mice. Ultra-fast cycling technology (FAST) was used for multi-cycle immunofluorescence of retrieved cells, and provided insights in the changing immune response over time. The combination of these techniques can be utilized to study changes in the immune response in glioma or other intracranial diseases over time, and in response to treatment within the same animal.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"57 ","pages":"Article 101051"},"PeriodicalIF":4.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000939/pdfft?md5=70d95fb8b4ab21e4f623ea1938070cd4&pid=1-s2.0-S1476558624000939-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142172093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ELAVL1 regulates PD-L1 mRNA stability to disrupt the infiltration of CD4-positive T cells in prostate cancer","authors":"Zhonglin Cai ,&nbsp;Xiuxia Zhai ,&nbsp;Jidong Xu ,&nbsp;Tianyu Hong ,&nbsp;Kuo Yang ,&nbsp;Shasha Min ,&nbsp;Jianuo Du ,&nbsp;Zhikang Cai ,&nbsp;Zhong Wang ,&nbsp;Ming Shen ,&nbsp;Di Wang ,&nbsp;Yanting Shen","doi":"10.1016/j.neo.2024.101049","DOIUrl":"10.1016/j.neo.2024.101049","url":null,"abstract":"<div><p>Prostate cancer (PCa) currently ranks second in male tumor mortality. Targeting immune checkpoint in tumor as immunotherapy is a new direction for tumor treatment. However, targeting PD-1/PD-L1 and CTLA4 to treat PCa has poor immunotherapeutic efficacy because PCa is known as a cold tumor. Understanding the mechanism of immunosuppression in PCa can promote the use of immunotherapy to treat PCa. ELAVL1 is highly expressed in many tumors, participates in almost all tumor biological activities and is an oncogene. ELAVL1 is also involved in the development and differentiation of T and B lymphocytes. However, the relationship between ELAVL1 and tumor immunity has not yet been reported. In recent years, ELAVL1 has been shown to regulate downstream targets in an m6A -dependent manner. PD-L1 has been shown to have m6A sites in multiple tumors that are regulated by m6A. In this study, ELAVL1 was highly expressed in PCa, and PCa with high ELAVL1 expression is immunosuppressive. Knocking down ELAVL1 reduced PD-L1 expression in PCa. Moreover, PD-L1 was shown to have an m6A site, and its m6A level was upregulated in PCa<em>.</em> ELAVL1 interacts with <em>PD-L1</em> mRNA and promotes <em>PD-L1</em> RNA stability via m6A, ultimately inhibiting the infiltration of CD4-positive T cells. In addition, androgen receptor (AR) was shown to be regulated with ELAVL1, and knocking down AR could also affect the expression of PD-L1. Therefore, ELAVL1 can directly or indirectly regulate the expression of PD-L1, thereby affecting the infiltration of CD4-positive T cells in PCa and ultimately leading to immune suppression.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"57 ","pages":"Article 101049"},"PeriodicalIF":4.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000915/pdfft?md5=231120b0aba4870e14a22dce496babe1&pid=1-s2.0-S1476558624000915-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142168784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the impact of SUMOylation at K298 site of heat shock factor 1 on glioblastoma malignant progression","authors":"Xiang Li ,&nbsp;Zongqi Wang ,&nbsp;Bixi Gao ,&nbsp;Kun Dai ,&nbsp;Jiang Wu ,&nbsp;Kecheng Shen ,&nbsp;Guangzhao Li ,&nbsp;Xiaowang Niu ,&nbsp;Xin Wu ,&nbsp;Longyuan Li ,&nbsp;Haitao Shen ,&nbsp;Haiying Li ,&nbsp;Zhengquan Yu ,&nbsp;Zhong Wang ,&nbsp;Gang Chen","doi":"10.1016/j.neo.2024.101055","DOIUrl":"10.1016/j.neo.2024.101055","url":null,"abstract":"<div><h3>Background</h3><p>Glioblastoma (GBM) poses a significant medical challenge due to its aggressive nature and poor prognosis. Mitochondrial unfolded protein response (UPRmt) and the heat shock factor 1 (HSF1) pathway play crucial roles in GBM pathogenesis. Post-translational modifications, such as SUMOylation, regulate the mechanism of action of HSF1 and may influence the progression of GBM. Understanding the interplay between SUMOylation-modified HSF1 and GBM pathophysiology is essential for developing targeted therapies.</p></div><div><h3>Methods</h3><p>We conducted a comprehensive investigation using cellular, molecular, and <em>in vivo</em> techniques. Cell culture experiments involved establishing stable cell lines, protein extraction, Western blotting, co-immunoprecipitation, and immunofluorescence analysis. Mass spectrometry was utilized for protein interaction studies. Computational modeling techniques were employed for protein structure analysis. Plasmid construction and lentiviral transfection facilitated the manipulation of HSF1 SUMOylation. <em>In vivo</em> studies employed xenograft models for tumor growth assessment.</p></div><div><h3>Results</h3><p>Our research findings indicate that HSF1 primarily undergoes SUMOylation at the lysine residue K298, enhancing its nuclear translocation, stability, and downstream heat shock protein expression, while having no effect on its trimer conformation. SUMOylated HSF1 promoted the UPRmt pathway, leading to increased GBM cell proliferation, migration, invasion, and reduced apoptosis. <em>In vivo</em> studies have confirmed that SUMOylation of HSF1 enhances its oncogenic effect in promoting tumor growth in GBM xenograft models.</p></div><div><h3>Conclusion</h3><p>This study elucidates the significance of SUMOylation modification of HSF1 in driving GBM progression. Targeting SUMOylated HSF1 may offer a novel therapeutic approach for GBM treatment. Further investigation into the specific molecular mechanisms influenced by SUMOylated HSF1 is warranted for the development of effective targeted therapies to improve outcomes for GBM patients.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"57 ","pages":"Article 101055"},"PeriodicalIF":4.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000964/pdfft?md5=b2f49cb5fb15f6a1e285a92769762dc7&pid=1-s2.0-S1476558624000964-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142162190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A highly selective PI3Kδ inhibitor BGB-10188 shows superior preclinical anti-tumor activities and decreased on-target side effects on colon","authors":"Xiao Yang,&nbsp;Huichen Bai,&nbsp;Xi Yuan,&nbsp;Xiaolong Yang,&nbsp;Ye Liu,&nbsp;Mingming Guo,&nbsp;Nan Hu,&nbsp;Beibei Jiang,&nbsp;Zeqin Lian,&nbsp;Zhilong Ma,&nbsp;Jingyuan Wang,&nbsp;Xuebing Sun,&nbsp;Taichang Zhang,&nbsp;Dan Su,&nbsp;Yue Wu,&nbsp;Jing Li,&nbsp;Fan Wang,&nbsp;Zhiwei Wang,&nbsp;Lai Wang,&nbsp;Xuesong Liu,&nbsp;Xiaomin Song","doi":"10.1016/j.neo.2024.101053","DOIUrl":"10.1016/j.neo.2024.101053","url":null,"abstract":"<div><p>PI3Kδ is a key signal transduction molecule in normal and malignant B cells, as well as in T-regulatory cells, making it a promising target for treatment of hematologic malignancies through both direct killing and anti-tumor immunity regulation. BGB-10188 is a highly selective inhibitor of PI3Kδ, showing more than 3000 folds selectivity over other PI3K isoforms and no significant inhibition across tested kinases. BGB-10188 potently inhibited PI3Kδ with IC₅₀s ranging from 1.7-16 nM through various <em>in vitro</em> assays and showed a long-lasting and strong target inhibition in mouse B cells <em>in vivo</em>. BGB-10188 showed significant antitumor effects in human B cell lymphoma xenograft models as single agent or in combination with the BTK inhibitor zanubrutinib. BGB-10188 showed significant Treg inhibition in blood but not in colon, along with less drug accumulation in colon compared with idelalisib, which is an approved PI3Kdelta inhibitor with high incidence of gastrointestinal side effects in clinic. In summary, BGB-10188 is a novel PI3Kδ inhibitor with high selectivity, potency and improved safety profile shown in preclinical studies, which is showing the potential as a best-in-class PI3Kδ inhibitor.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"57 ","pages":"Article 101053"},"PeriodicalIF":4.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000952/pdfft?md5=41afa871bf66349289dfdcfab36446af&pid=1-s2.0-S1476558624000952-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142162191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FABP4 facilitates epithelial-mesenchymal transition via elevating CD36 expression in glioma cells","authors":"Zhongsheng You ,&nbsp;Zihao Hu ,&nbsp;Chongxian Hou ,&nbsp;Chengcheng Ma ,&nbsp;Xiangdong Xu ,&nbsp;Yaofeng Zheng ,&nbsp;Xinlin Sun ,&nbsp;Yiquan Ke ,&nbsp;Jianli Liang ,&nbsp;Zijing Xie ,&nbsp;Lingling Shu ,&nbsp;Yang Liu","doi":"10.1016/j.neo.2024.101050","DOIUrl":"10.1016/j.neo.2024.101050","url":null,"abstract":"<div><p>Glioblastoma multiforme (GBM) is the most aggressive brain tumor with poor prognosis. A better understanding of mechanisms concerned in glioma invasion might be critical for treatment optimization. Given that epithelial-mesenchymal transition in tumor cells is closely associated with glioma progression and recurrence, identifying pivotal mediators in GBM EMT process is urgently needed. As a member of Fatty acid binding protein (FABP) family, FABP4 serves as chaperones for free fatty acids and participates in cellular process including fatty acid uptake, transport, and metabolism. In this study, our data revealed that FABP4 expression was elevated in human GBM samples and correlated with a mesenchymal glioma subtype. Gain of function and loss of function experiments indicated that FABP4 potently rendered glioma cells increased filopodia formation and cell invasiveness. Differential expression genes analysis and GSEA in TCGA dataset revealed an EMT-related molecular signature in FABP4-mediated signaling pathways. Cell interaction analysis suggested CD36 as a potential target regulated by FABP4. Furthermore, <em>in vitro</em> mechanistic experiments demonstrated that FABP4-induced CD36 expression promoted EMT via non-canonical TGFβ pathways. An intracranial glioma model was constructed to assess the effect of FABP4 on tumor progression <em>in vivo</em>. Together, our findings demonstrated a critical role for FABP4 in the regulation invasion and EMT in GBM, and suggest that pharmacological inhibition of FABP4 may represent a promising therapeutic strategy for treatment of GBM.</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"57 ","pages":"Article 101050"},"PeriodicalIF":4.8,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000927/pdfft?md5=cf4df34bcae3cf715a8da2c16b435078&pid=1-s2.0-S1476558624000927-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of prostate-specific membrane antigen (PSMA) expression in prostate cancer cells after treatment with dutasteride and lovastatin","authors":"Aleksandar Kuzmanov,&nbsp;Souzan Salemi,&nbsp;Daniel Eberli,&nbsp;Benedikt Kranzbühler","doi":"10.1016/j.neo.2024.101045","DOIUrl":"10.1016/j.neo.2024.101045","url":null,"abstract":"<div><p>PSMA expression gradually increases from benign prostatic hyperplasia to adenocarcinoma of the prostate and is therefore used for the development of improved diagnostic (PSMA)‐based prostate cancer imaging tools. Pharmacological induction of PSMA is therefore eminent to further improve the detection rate of PSMA-based imaging. Our previous studies have demonstrated that lovastatin (Lova) and dutasteride (Duta) are able to induce PSMA expression. However, the mechanisms by which PSMA is regulated in prostate cancer remain poorly understood. Androgen receptor (AR) and homeobox B13 (HOXB13) are the best known regulators of PSMA, hence in the present study we aimed to explore the PSMA regulation by HOXB13 and AR signaling in LNCaP and VCaP cells following treatments with Lova and Duta. Furthermore, our previous research revealed a growth arrest in prostate cancer cells after Lova, but not after Duta treatment. To understand this discrepancy, we explored the influence of Lova and Duta on well known tumor growth promoters, such as AR, the mTOR/Akt signaling pathways and Cyclin D1. Our results showed that treatment with Lova leads to a significant inhibition of the investigated tumor promoters and results in growth regression of LNCaP and VCaP cells. In contrast, Duta does not show these effects. Furthermore, we confirm the cooperative effect of HOXB13 and AR in regulating PSMA in LNCaP cells, and extend the investigations to an additional prostate cancer cell line (VCaP).</p></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"57 ","pages":"Article 101045"},"PeriodicalIF":4.8,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1476558624000873/pdfft?md5=9afd6a0905160461c05068e75f7f8b9b&pid=1-s2.0-S1476558624000873-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142136312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}