Cellular Oncology最新文献

{"title":"Hedgehog ligand and receptor cooperatively regulate EGFR stability and activity in non-small cell lung cancer","authors":"Aidi Huang, Junyao Cheng, Yuan Zhan, Feifei Zhou, Yanlu Xuan, Yiting Wang, Qingjie Chen, Hailong Wang, Xinping Xu, Shiwen Luo, Minzhang Cheng","doi":"10.1007/s13402-024-00938-6","DOIUrl":"https://doi.org/10.1007/s13402-024-00938-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>The hyperactivation of epidermal growth factor receptor (EGFR) plays a crucial role in non-small cell lung cancer (NSCLC). Hedgehog (Hh) signaling has been implicated in the tumorigenesis and progression of various cancers, however, its function in NSCLC cells remains controversial. Herein, we present a novel finding that challenges the current understanding of Hh signaling in tumor growth.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Expression of Hh ligands and receptor were assessed using TCGA datasets, immunoblotting and immunohistochemical. Biological function of Hh ligands and receptor in NSCLC were tested using colony formation, cell count kit-8 (CCK-8) and xenograft assays. Biochemical effect of Hh ligands and receptor on regulating EGFR stability and activity were checked via immunoblotting.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Expression of Hh ligands and receptor was suppressed in NSCLC tissues, and the lower expression levels of these genes were associated with poor prognosis. Ptch1 binds to EGFR and facilitates its poly-ubiquitylation and degradation independent of downstream transcriptional signaling. Moreover, Hh ligands cooperate with Ptch1 to regulate the protein stability and activity of EGFR. This unique mechanism leads to a suppressive effect on NSCLC tumor growth.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Non-canonical Hh signaling pathway, involving cooperation between Hh ligands and their receptor Ptch1, facilitates the degradation of EGFR and attenuates its activity in NSCLC. These findings provide novel insights into the regulation of EGFR protein stability and activity, offer new diagnostic indicators for molecular typing of NSCLC and identify potential targets for targeted therapy of this challenging disease.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":"105 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140579529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The microbiota and renal cell carcinoma.","authors":"Ke Wu, Yaorong Li, Kangli Ma, Weiguang Zhao, Zhixian Yao, Zhong Zheng, Feng Sun, Xingyu Mu, Zhihong Liu, Junhua Zheng","doi":"10.1007/s13402-023-00876-9","DOIUrl":"10.1007/s13402-023-00876-9","url":null,"abstract":"<p><p>Renal cell carcinoma (RCC) accounts for about 2% of cancer diagnoses and deaths worldwide. Recent studies emphasized the critical involvement of microbial populations in RCC from oncogenesis, tumor growth, and response to anticancer therapy. Microorganisms have been shown to be involved in various renal physiological and pathological processes by influencing the immune system function, metabolism of the host and pharmaceutical reactions. These findings have extended our understanding and provided more possibilities for the diagnostic or therapeutic development of microbiota, which could function as screening, prognostic, and predictive biomarkers, or be manipulated to prevent RCC progression, boost anticancer drug efficacy and lessen the side effects of therapy. This review aims to present an overview of the roles of microbiota in RCC, including pertinent mechanisms in microbiota-related carcinogenesis, the potential use of the microbiota as RCC biomarkers, and the possibility of modifying the microbiota for RCC prevention or treatment. According to these scientific findings, the clinical translation of microbiota is expected to improve the diagnosis and treatment of RCC.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":"397-413"},"PeriodicalIF":6.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50157137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FAP is a prognostic marker, but not a viable therapeutic target for clinical translation in HNSCC.","authors":"Jie Liu, Yeling Ouyang, Zijin Xia, Wenhao Mai, Hongrui Song, Fang Zhou, Lichun Shen, Kaiting Chen, Xiaochen Li, Shi-Min Zhuang, Jing Liao","doi":"10.1007/s13402-023-00888-5","DOIUrl":"10.1007/s13402-023-00888-5","url":null,"abstract":"<p><strong>Purpose: </strong>PD-1 targeted immunotherapy has imparted a survival benefit to advanced head and neck squamous cell carcinoma (HNSCC), but less than 20% patients produce a durable response to this therapy. Here we aimed to investigate the potential biomarkers for predicting the clinical outcome and resistance to PD-1 targeted immunotherapy in HNSCC patients, and to examine the involvement of FAP⁺ cancer-associated fibroblasts (CAFs).</p><p><strong>Methods: </strong>Bioinformatics methods were applied to analyze multiple datasets and explore the role of PD-1 and FAP in HNSCC. Immunohistochemistry was used to detect the expression of FAP protein. Fap gene knockout mice (Fap^-/-) and L929 cells with different levels of Fap overexpression (L929-Fap-Low/High) were established to demonstrate the role of FAP⁺ CAFs in tumor development and immune checkpoint blockade (ICB) resistance.</p><p><strong>Results: </strong>The expression level of PD-1 gene was positively correlated with better overall survival and therapeutic response to PD-1 blockade in HNSCC, but not all tumors with high expression of both PD-1 and PD-L1 were responsive. Moreover, FAP gene was overexpressed in pan-cancer tissues, and could serve as a prognostic biomarker for several cancers, including HNSCC. However, FAP protein was undetectable in mouse MTCQ1 tumors and barely expressed in human HNSCC tumors. Furthermore, FAP⁺ CAFs did not promote tumor growth or enhance the resistance to PD-1 inhibitor treatment.</p><p><strong>Conclusion: </strong>Although FAP⁺ CAFs have attracted increasing attention for their role in cancer, the feasibility and efficacy of FAP-targeting therapies for HNSCC remain doubtful.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":"623-638"},"PeriodicalIF":6.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49674707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The leukemia inhibitory factor regulates fibroblast growth factor receptor 4 transcription in gastric cancer.","authors":"Cristina Di Giorgio, Rachele Bellini, Antonio Lupia, Carmen Massa, Ginevra Urbani, Martina Bordoni, Silvia Marchianò, Rosalinda Rosselli, Rosa De Gregorio, Pasquale Rapacciuolo, Valentina Sepe, Elva Morretta, Maria Chiara Monti, Federica Moraca, Luigi Cari, Khan Rana Sami Ullah, Nicola Natalizi, Luigina Graziosi, Eleonora Distrutti, Michele Biagioli, Bruno Catalanotti, Annibale Donini, Angela Zampella, Stefano Fiorucci","doi":"10.1007/s13402-023-00893-8","DOIUrl":"10.1007/s13402-023-00893-8","url":null,"abstract":"<p><strong>Purpose: </strong>The gastric adenocarcinoma (GC) represents the third cause of cancer-related mortality worldwide, and available therapeutic options remain sub-optimal. The Fibroblast growth factor receptors (FGFRs) are oncogenic transmembrane tyrosine kinase receptors. FGFR inhibitors have been approved for the treatment of various cancers and a STAT3-dependent regulation of FGFR4 has been documented in the H.pylori infected intestinal GC. Therefore, the modulation of FGFR4 might be useful for the treatment of GC.</p><p><strong>Methods: </strong>To investigate wich factors could modulate FGFR4 signalling in GC, we employed RNA-seq analysis on GC patients biopsies, human patients derived organoids (PDOs) and cancer cell lines.</p><p><strong>Results: </strong>We report that FGFR4 expression/function is regulated by the leukemia inhibitory factor (LIF) an IL-6 related oncogenic cytokine, in JAK1/STAT3 dependent manner. The transcriptomic analysis revealed a direct correlation between the expression of LIFR and FGFR4 in the tissue of an exploratory cohort of 31 GC and confirmed these findings by two external validation cohorts of GC. A LIFR inhibitor (LIR-201) abrogates STAT3 phosphorylation induced by LIF as well as recruitment of pSTAT3 to the promoter of FGFR4. Furthermore, inhibition of FGFR4 by roblitinib or siRNA abrogates STAT3 phosphorylation and oncogentic effects of LIF in GC cells, indicating that FGFR4 is a downstream target of LIF/LIFR complex. Treating cells with LIR-201 abrogates oncogenic potential of FGF19, the physiological ligand of FGFR4.</p><p><strong>Conclusions: </strong>Together these data unreveal a previously unregnized regulatory mechanism of FGFR4 by LIF/LIFR and demonstrate that LIF and FGF19 converge on the regulation of oncogenic STAT3 in GC cells.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":"695-710"},"PeriodicalIF":6.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11090936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72013629","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":"Multi-dimensional characterization of apoptosis in the tumor microenvironment and therapeutic relevance in melanoma","authors":"Jing Ye, Benliang Wei, Guowei Zhou, Yantao Xu, Yi He, Xiheng Hu, Xiang Chen, Guanxiong Zhang, Hong Liu","doi":"10.1007/s13402-024-00930-0","DOIUrl":"https://doi.org/10.1007/s13402-024-00930-0","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Melanoma is widely utilized as a prominent model for the development of immunotherapy, thought an inadequate immune response can occur. Moreover, the development of apoptosis-related therapies and combinations with other therapeutic strategies is impeded by the limited understanding of apoptosis’s role within diverse tumor immune microenvironments (TMEs).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Here, we constructed an apoptosis-related tumor microenvironment signature (ATM) and employ multi-dimensional analysis to understand the roles of apoptosis in tumor microenvironment. We further assessed the clinical applications of ATM in nine independent cohorts, and anticipated the impact of ATM on cellular drug response in cultured cells.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Our ATM model exhibits robust performance in survival prediction in multiple melanoma cohorts. Different ATM groups exhibited distinct molecular signatures and biological processes. The low ATM group exhibited significant enrichment in B cell activation-related pathways. What’s more, plasma cells showed the lowest ATM score, highlighting their role as pivotal contributors in the ATM model. Mechanistically, the analysis of the interplay between plasma cells and other immune cells elucidated their crucial role in orchestrating an effective anti-tumor immune response. Significantly, the ATM signature exhibited associations with therapeutic efficacy of immune checkpoint blockade and the drug sensitivity of various agents, including FDA-approved and clinically utilized drugs targeting the VEGF signaling pathway. Finally, ATM was associated with tertiary lymphoid structures (TLS), exhibiting stronger patient stratification ability compared to classical “hot tumors”.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Our findings indicate that ATM is a prognostic factor and is associated with the immune response and drug sensitivity in melanoma.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":"3 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140165962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Ribonuclease ZC3H12A is required for self-inflicted DNA breaks after DNA damage in small cell lung cancer cells","authors":"Mingjun Lu, Qing Gao, Renjing Jin, Meng Gu, Ziyu Wang, Xiaobo Li, Weiying Li, Jinghui Wang, Teng Ma","doi":"10.1007/s13402-024-00941-x","DOIUrl":"https://doi.org/10.1007/s13402-024-00941-x","url":null,"abstract":"<p>Radiotherapy is the first line treatment for small cell lung cancer (SCLC); However, radio-resistance accompanies with the treatment and hampers the prognosis for SCLC patients. The underlying mechanisms remains elusive. Here we discovered that self-inflicted DNA breaks exist in SCLC cells after radiation. Moreover, using nuclease siRNA screening combined with high-content ArrayScan™ cell analyzer, we identified that Ribonuclease ZC3H12A is required for the self-inflicted DNA breaks after radiation and for SCLC cell survival after DNA damage. ZC3H12A expression was increased in response to DNA damage and when ZC3H12A was knocked down, the DNA repair ability of the cells was impaired, as evidenced by decreased expression of the DNA damage repair protein BRCA1, and increased γH2AX at DNA damage sites. Colony formation assay demonstrates that ZC3H12A knocked down sensitized small cell lung cancer radiotherapy. Therefore, the Ribonuclease ZC3H12A regulates endogenous secondary breaks in small cell lung cancer and affects DNA damage repair. ZC3H12A may act as an important radiotherapy target in small cell lung cancer.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":"27 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140151709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prognostic effect of tumor-associated macrophages in stage I-III colorectal cancer depends on T cell infiltration","authors":"Umair Majid, Christian Holst Bergsland, Anita Sveen, Jarle Bruun, Ina Andrassy Eilertsen, Espen S. Bækkevold, Arild Nesbakken, Sheraz Yaqub, Frode L. Jahnsen, Ragnhild A. Lothe","doi":"10.1007/s13402-024-00926-w","DOIUrl":"https://doi.org/10.1007/s13402-024-00926-w","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Tumor-associated macrophages (TAMs) are associated with unfavorable patient prognosis in many cancer types. However, TAMs are a heterogeneous cell population and subsets have been shown to activate tumor-infiltrating T cells and confer a good patient prognosis. Data on the prognostic value of TAMs in colorectal cancer are conflicting. We investigated the prognostic effect of TAMs in relation to tumor-infiltrating T cells in colorectal cancers.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>The TAM markers CD68 and CD163 were analyzed by multiplex fluorescence immunohistochemistry and digital image analysis on tissue microarrays of 1720 primary colorectal cancers. TAM density in the tumor stroma was scored in relation to T cell density (stromal CD3⁺ and epithelial CD8⁺ cells) and analyzed in Cox proportional hazards models of 5-year relapse-free survival. Multivariable survival models included clinicopathological factors, MSI status and <i>BRAF</i>^V600E mutation status.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>High TAM density was associated with a favorable 5-year relapse-free survival in a multivariable model of patients with stage I–III tumors (<i>p</i> = 0.004, hazard ratio 0.94, 95% confidence interval 0.90–0.98). However, the prognostic effect was dependent on tumoral T-cell density. High TAM density was associated with a good prognosis in patients who also had high T-cell levels in their tumors, while high TAM density was associated with poorer prognosis in patients with low T-cell levels (<i>p</i>_interaction = 0.0006). This prognostic heterogeneity was found for microsatellite stable tumors separately.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>This study supported a phenotypic heterogeneity of TAMs in colorectal cancer, and showed that combined tumor immunophenotyping of multiple immune cell types improved the prediction of patient prognosis.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":"2014 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139968248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GDF15 induces chemoresistance to oxaliplatin by forming a reciprocal feedback loop with Nrf2 to maintain redox homeostasis in colorectal cancer","authors":"Haiping Lin, Yang Luo, Tingyue Gong, Hongsheng Fang, Hao Li, Guangyao Ye, Yan Zhang, Ming Zhong","doi":"10.1007/s13402-024-00918-w","DOIUrl":"https://doi.org/10.1007/s13402-024-00918-w","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Growth differentiating Factor 15 (GDF15) is linked to several cancers, but its effect on chemoresistance in colorectal cancer (CRC) remains unclear. Here, we investigated the role of GDF15 in the chemotherapeutic response of CRC patients to oxaliplatin (L-OHP).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>GDF15 levels in serum and tumour tissues were detected in CRC patients have received L-OHP-based neoadjuvant chemotherapy. The effects of GDF15 neutralization or GDF15 knockdown on cell proliferation, apoptosis and intracellular reactive oxygen species (ROS) levels were analysed in vitro and in vivo. Co-immunoprecipitation (Co-IP), Chromatin Immunoprecipitation (ChIP) and luciferase reporter assays were used to explore the interaction between GDF15 and Nrf2.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>In this study, we found that GDF15 alleviates oxidative stress to induce chemoresistance of L-OHP in CRC. Mechanically, GDF15 posttranscriptionally regulates protein stability of Nrf2 through the canonical PI3K/AKT/GSK3β signaling pathway, and in turn, Nrf2 acts as a transcription factor to regulate GDF15 expression to form a positive feedback loop, resulting in the maintenance of redox homeostasis balance in CRC. Furthermore, a positive correlation between GDF15 and Nrf2 was observed in clinical CRC samples, and simultaneous overexpression of both GDF15 and Nrf2 was associated with poor prognosis in CRC patients treated with L-OHP. Simultaneous inhibition of both GDF15 and Nrf2 significantly increases the response to L-OHP in an L-OHP-resistant colorectal cancer cells-derived mouse xenograft model.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>This study identified a novel GDF15-Nrf2 positive feedback loop that drives L-OHP resistance and suggested that the GDF15-Nrf2 axis is a potential therapeutic target for the treatment of L-OHP-resistant CRC.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":"26 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139919693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PIN1 promotes the metastasis of cholangiocarcinoma cells by RACK1-mediated phosphorylation of ANXA2","authors":"Yuming Wang, Yiwei Liu, Hairong Chen, Zhenggang Xu, Wangjie Jiang, Xiao Xu, Jijun Shan, Jiang Chang, Tao Zhou, Jifei Wang, Anlan Chenyan, Shilong Fan, Zifan Tao, Ke Shao, Xiangcheng Li, Xiaofeng Chen, Guwei Ji, Xiaofeng Wu","doi":"10.1007/s13402-024-00924-y","DOIUrl":"https://doi.org/10.1007/s13402-024-00924-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Cholangiocarcinoma (CCA), a primary hepatobiliary malignancy, is characterized by a poor prognosis and a lack of effective treatments. Therefore, the need to explore novel therapeutic approaches is urgent. While the role of Peptidylprolyl Cis/Trans Isomerase, NIMA-Interacting 1 (PIN1) has been extensively studied in various tumor types, its involvement in CCA remains poorly understood.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>In this study, we employed tissue microarray (TMA), reverse transcription-polymerase chain reaction (RT-PCR), and The Cancer Genome Atlas (TCGA) database to assess the expression of PIN1. Through in vitro and in vivo functional experiments, we investigated the impact of PIN1 on the adhesion and metastasis of CCA. Additionally, we explored downstream molecular pathways using RNA-seq, western blotting, co-immunoprecipitation, immunofluorescence, and mass spectrometry techniques.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Our findings revealed a negative correlation between PIN1 overexpression and prognosis in CCA tissues. Furthermore, high PIN1 expression promoted CCA cell proliferation and migration. Mechanistically, PIN1 functioned as an oncogene by regulating ANXA2 phosphorylation, thereby promoting CCA adhesion. Notably, the interaction between PIN1 and ANXA2 was facilitated by RACK1. Importantly, pharmacological inhibition of PIN1 using the FDA-approved drug all-trans retinoic acid (ATRA) effectively suppressed the metastatic potential of CCA cells in a nude mouse lung metastasis model.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Overall, our study emphasizes the critical role of the PIN1/RACK1/ANXA2 complex in CCA growth and functionality, highlighting the potential of targeting PIN1 as a promising therapeutic strategy for CCA.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":"28 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139919727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles related gene HSPH1 exerts anti-tumor effects in prostate cancer via promoting the stress response of CD8 + T cells","authors":"","doi":"10.1007/s13402-023-00905-7","DOIUrl":"https://doi.org/10.1007/s13402-023-00905-7","url":null,"abstract":"<h3>Abstract</h3> <span> <h3>Background</h3> <p>T cell stress response state (TSTR), as a novel immune concept previous studies have proposed, has not yet been explored in prostate cancer (PC). As a type of cellular efflux, exosomes play important roles in the occurrence and development of PC.</p> </span> <span> <h3>Method</h3> <p>Here, we conducted a combined analysis on extracellular vesicle related genes (EVRGs) in PC using data from single-cell RNA (scRNA), spatial transcriptome (ST), and bulk RNA sequencing.</p> </span> <span> <h3>Result</h3> <p>Preliminary findings have revealed that heat shock protein family H (Hsp110) member 1 (HSPH1) possesses two identities, one being EVRGs and the other being a member of the heat shock protein family involved in TSTR, which may promote the differentiation of conventional T cells towards Th1 or Th2 cells through the pathway of IL2-MYC-IL2RA, thereby promoting the increase of CD8 + T cells in the tumor area, especially in the invasive zone, and inhibiting the invasion of PCs. We also notice the negative response of HSPH1 + CD8 + T cell related genes in immune checkpoint blockade (ICB). Western blot (WB) and droplet digital Polymerase Chain Reaction (ddPCR) demonstrated that the mRNA and protein levels of HSPH1 in EVs of PCs were significantly higher than those in adjacent tissues.</p> </span> <span> <h3>Conclusion</h3> <p>Results above indicate the potential of HSPH1 as a critical therapeutic target in PC.</p> </span>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":"9 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139078519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}