Cancer Science最新文献

{"title":"Opportunities to Modulate Tumor Ecosystem Toward Successful Glioblastoma Immunotherapy","authors":"Mariko Takahashi,&nbsp;Darina Mukhamejanova,&nbsp;Himani Jasewicz,&nbsp;Nandini Acharya,&nbsp;James J. Moon,&nbsp;Toshiro Hara","doi":"10.1111/cas.70052","DOIUrl":"10.1111/cas.70052","url":null,"abstract":"<p>Over the past decade, the failure of multiple clinical trials has confirmed the need for a systematic and comprehensive understanding of glioblastoma (GBM). Current immunotherapies aiming to harness the immune system to achieve anti-tumor effects remain largely ineffective, highlighting the complexities of the GBM microenvironment. However, our recent understanding of immune niches within the central nervous system provides both opportunities and challenges in translating these insights into successful immunotherapy implementation. We discuss these strategies, including targeting multiple antigens within the heterogeneous GBM microenvironment, identifying new druggable targets to abrogate immunosuppression, and understanding niche-specific immune cell functionality to modulate tumor-immune-stroma interactions.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 6","pages":"1482-1499"},"PeriodicalIF":4.5,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694247","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":"VCP Promotes Cholangiocarcinoma Development by Mediating BAP1 Ubiquitination-Dependent Degradation","authors":"Peiying Zhang,&nbsp;Xiangning Liu,&nbsp;Yue Liu,&nbsp;Hongdao Zhu,&nbsp;Churun Zheng,&nbsp;Qi Ling,&nbsp;Fangjie Yan,&nbsp;Qiaojun He,&nbsp;Hong Zhu,&nbsp;Tao Yuan,&nbsp;Bo Yang","doi":"10.1111/cas.70061","DOIUrl":"10.1111/cas.70061","url":null,"abstract":"<p>Cholangiocarcinoma (CCA), recognized for its high malignancy, has been an enormous challenge due to lacking effective treatment therapy over the past decades. Recently, the targeted therapies, such as Pemigatinib and Ivosidenib, have provided new treatment options for patients carrying fibroblast growth factor receptor (FGFR) and isocitrate dehydrogenase 1/2 (IDH1/2) mutations, but only ~30% of patients harbor these mutants; it is urgent to explore novel targets and therapeutic therapies. The frequent downregulation of BAP1 has been observed in CCA, and the low expression of BAP1 is closely related to the poor prognosis of CCA. However, there are no effective interventions to re-activate BAP1 protein; blocking its degradation may provide a feasible strategy for BAP1-downregulation CCA treatment. In this study, we demonstrated the tumor-suppressive roles of BAP1 in CCA and identified VCP functions as the key upstream regulator mediated by BAP1 protein homeostasis. Mechanistically, VCP binds to BAP1 and promotes the latter's ubiquitination degradation via the ubiquitin-proteasome pathway, thus promoting cell proliferation and inhibiting cell apoptosis. Moreover, we found that VCP inhibitors inhibited CCA cell growth and promoted cell apoptosis by blocking BAP1 ubiquitination degradation. Collectively, our findings not only provided a novel mechanism underlying the aberrant low expression of BAP1 in CCA but also verified the anti-tumor effect of VCP inhibitors in CCA, offering a novel therapeutic target for CCA treatment.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 6","pages":"1579-1591"},"PeriodicalIF":4.5,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694248","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":"Epacadostat Overcomes Cetuximab Resistance in Colorectal Cancer by Targeting IDO-Mediated Tryptophan Metabolism","authors":"Yimin Zhou,&nbsp;Qiongyan Tao,&nbsp;Chubin Luo,&nbsp;Jinsong Chen,&nbsp;Genwen Chen,&nbsp;Jianyong Sun","doi":"10.1111/cas.70057","DOIUrl":"10.1111/cas.70057","url":null,"abstract":"<p>Primary or acquired mutations in RAS/RAF genes resulting in cetuximab resistance have limited its clinical application in colorectal cancer (CRC) patients. The mechanism of this resistance remains unclear. RNA sequencing from cetuximab-sensitive and -resistant specimens revealed an activation of the tryptophan pathway and elevation of IDO1 and IDO2 in cetuximab-resistant CRC patients. In vitro, in vivo, and clinical specimens confirmed the upregulation of IDO1and IDO2 and the Kyn/Trp after cetuximab treatment. Additionally, the IDO inhibitor, epacadostat, could effectively inhibit the migration and proliferation of cetuximab-resistant CRC cells while promoting apoptosis. Compared to epacadostat monotherapy, the combination of cetuximab and epacadostat showed a stronger synergistic anti-tumor effect. Furthermore, in vivo experiments confirmed that combination therapy effectively suppressed tumor growth. Mechanistically, KEGG pathway analysis revealed the activation of the IFN-γ pathway in cetuximab-resistant CRC tissues. Luciferase reporter assays confirmed the transcriptional activity of IDO1 following cetuximab treatment. Silencing IFN-γ then suppressed the upregulation induced by cetuximab. Moreover, we observed that the combination reduced the concentration of the tryptophan metabolite kynurenine, promoted the infiltration of CD8⁺ T lymphocytes, and enhanced the polarization of M1 macrophages within the tumor microenvironment, thereby exerting potent anti-tumor immune effects. Overall, our results confirm the remarkable therapeutic efficacy of combining cetuximab with epacadostat in cetuximab-resistant CRC. Our findings may provide a novel target for overcoming cetuximab resistance in CRC.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 6","pages":"1715-1729"},"PeriodicalIF":4.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659389","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":"Spatial Heterogeneity of PD-L1 Expression as a Biomarker for Third-Generation EGFR-TKI Response in Advanced EGFR-Mutant NSCLC","authors":"Yidan Zhang,&nbsp;Yingqi Xu,&nbsp;Hongping Jin,&nbsp;Tengfei Liu,&nbsp;Hua Zhong,&nbsp;Jianlin Xu,&nbsp;Yuqing Lou,&nbsp;Runbo Zhong","doi":"10.1111/cas.70060","DOIUrl":"10.1111/cas.70060","url":null,"abstract":"<p>The association between the spatial heterogeneity of programmed cell death ligand 1 (PD-L1) expression and the efficacy of third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC) remains elusive. This retrospective study analyzed data from 4171 NSCLC patients with EGFR-sensitive mutations treated at Shanghai Chest Hospital from August 2019 to September 2023. Among them, 182 patients receiving third-generation EGFR-TKIs monotherapy as a first-line treatment were enrolled. Patients were categorized by biopsy sites into primary lung lesions (<i>n</i> = 112) and metastatic lymph nodes (<i>n</i> = 70). PD-L1 expression was stratified based on tumor cell proportion score (TPS): &lt; 1%, 1%–49%, and ≥ 50%. The median progression-free survival (PFS) for the entire cohort was 18.33 months. In the PD-L1 TPS group, PFS was 18.87 months for TPS &lt; 1%, 17.6 months for TPS 1%–49%, and 13.6 months for TPS ≥ 50%, with significant differences across groups (<i>p</i> = 0.026). Moreover, multivariate analysis identified smoking history [HR = 1.653, 95% CI (1.132–2.414), <i>p</i> = 0.009] and TPS ≥ 50% [HR = 2.069, 95% CI (1.183–3.618), <i>p</i> = 0.011] as independent risk factors. In primary lesions, the median PFS was 21.93 months for TPS &lt; 1%, 18.57 months for TPS 1%–49%, and 10.17 months for TPS ≥ 50%, with significant differences (<i>p</i> &lt; 0.001). However, PD-L1 expression in metastatic lymph nodes was not associated with PFS (<i>p</i> = 0.973). In advanced EGFR-mutant NSCLC, high PD-L1 expression may suggest reduced efficacy of third-generation EGFR-TKIs. The spatial heterogeneity of PD-L1 expression could influence its predictive accuracy for third-generation EGFR-TKI efficacy.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 6","pages":"1648-1660"},"PeriodicalIF":4.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659409","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":"Olaparib Plus Abiraterone in Asian Patients With Metastatic Castration-Resistant Prostate Cancer: PROpel Subset Analysis","authors":"Mototsugu Oya,&nbsp;Jae Young Joung,&nbsp;Ji Youl Lee,&nbsp;Mikio Sugimoto,&nbsp;Young Deuk Choi,&nbsp;Jun Hyuk Hong,&nbsp;Hiroji Uemura,&nbsp;Kazuo Nishimura,&nbsp;Hideyasu Tsumura,&nbsp;Satoru Kawakami,&nbsp;Yukiyoshi Hirayama,&nbsp;Tae Gyun Kwon,&nbsp;Cheol Kwak,&nbsp;Hiroyoshi Suzuki,&nbsp;Tomoko Fujita,&nbsp;Masahiro Nii,&nbsp;David McGuinness,&nbsp;Melanie Dujka,&nbsp;Christian Poehlein,&nbsp;Fred Saad,&nbsp;Noel Clarke","doi":"10.1111/cas.16459","DOIUrl":"10.1111/cas.16459","url":null,"abstract":"<p>In the phase 3 PROpel trial (NCT03732820) patients with metastatic castration-resistant prostate cancer (mCRPC) treated with olaparib plus abiraterone in the first-line setting showed significantly prolonged radiographic progression-free survival (rPFS; primary data cutoff [DCO]: 30 July 2021; hazard ratio [HR] 0.66, 95% confidence interval [CI], 0.54–0.81; <i>p</i> &lt; 0.001), and at prespecified final OS analysis DCO (12 October 2022) numerically prolonged overall survival (OS; HR 0.81, 95% CI, 0.67–1.00; <i>p</i> = 0.054), versus placebo plus abiraterone for the global population. Here, we report efficacy, safety, and patient-reported outcome data for the Asian subset in PROpel. Eligible patients were randomly assigned (1:1) to either olaparib (300 mg twice daily) or placebo in combination with abiraterone (1000 mg once daily). The primary endpoint was investigator-assessed rPFS, and a key secondary endpoint was OS. In the Asian subset (<i>n</i> = 133) at primary analysis, median rPFS was 27.6 months in the olaparib plus abiraterone arm (<i>n</i> = 63), compared with 19.3 months in the placebo plus abiraterone arm (<i>n</i> = 70; HR 0.55, 95% CI, 0.32–0.95). Median OS at the final analysis was not reached in the olaparib plus abiraterone arm versus 43.7 months in the placebo plus abiraterone arm (HR 0.59, 95% CI, 0.32–1.06). The safety profile was generally similar in the Asian subset and the global population. Efficacy and safety results for olaparib plus abiraterone in the Asian subset were generally consistent with the global PROpel population supporting the combination of olaparib plus abiraterone as an important first-line treatment for consideration in Asian patients with mCRPC.</p><p><b>Trial Registration:</b> Clinicaltrials.gov identifier: NCT03732820</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 6","pages":"1638-1647"},"PeriodicalIF":4.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16459","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659403","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":"Lnc-TPT1-AS1/CBP/ATIC Axis Mediated Purine Metabolism Activation Promotes Breast Cancer Progression","authors":"Yiyun Zhang,&nbsp;Hanyu Zhang,&nbsp;Mingcui Li,&nbsp;Yanling Li,&nbsp;Zhuo-Ran Wang,&nbsp;Weilun Cheng,&nbsp;Yansong Liu,&nbsp;Zhengbo Fang,&nbsp;Ang Zheng,&nbsp;Jingxuan Wang,&nbsp;Fei Ma","doi":"10.1111/cas.70045","DOIUrl":"10.1111/cas.70045","url":null,"abstract":"<p>The purine biosynthetic pathway was recently identified to play a crucial role in breast cancer progression. However, little was known about the regulatory mechanisms of long non-coding RNA in breast cancer purine metabolism. In this study, we discovered that LncRNA TPT1-AS1 (TPT1-AS1) was downregulated in breast cancer tissues. Its introduction in breast cancer cells markedly suppressed tumor growth and metastasis in xenograft tumor models. Mass spectrometric analysis suggested that the purine biosynthetic pathway was activated in TPT1-AS1-knockdown MCF-7 cells. Inosine monophosphate (IMP), the product of de novo purine biosynthesis, was significantly upregulated. Mechanistically, we found that TPT1-AS1 could physically interact with CBP (CREB-binding protein), which consequently led to the loss of H3K27Ac in the promoter area of ATIC, the key enzyme of IMP synthesis. This process could block breast cancer purine metabolism and inhibit breast cancer progression. In conclusion, our findings illustrate the role of non-coding RNAs in breast cancer purine metabolism reprogramming and present a potential candidate for breast cancer therapy.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 6","pages":"1565-1578"},"PeriodicalIF":4.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651500","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":"AmNA-Modified Antisense Oligonucleotide Targeting MCM8 as a Cancer-Specific Chemosensitizer for Platinum Compounds","authors":"Yuki Uchibori,&nbsp;Masaki Suekuni,&nbsp;Yuko Kokaji,&nbsp;Kazumasa Yoshida,&nbsp;Tohru Kiyono,&nbsp;Yuuya Kasahara,&nbsp;Masatoshi Fujita","doi":"10.1111/cas.70024","DOIUrl":"10.1111/cas.70024","url":null,"abstract":"<p>MCM8 and MCM9 participate in homologous recombination with long-tract gene conversion to repair double-strand breaks caused by replication stress, which is generally higher in cancer cells than in normal cells. MCM8 is highly expressed in certain cancer cells, where it is necessary for maintaining cell growth, migration, and invasion, although the molecular mechanisms remain unclear. Knockdown with siRNAs or knockout of MCM8 or MCM9 selectively sensitizes cancer cells to cisplatin. Thus, drugs inhibiting MCM8 or MCM9 could serve as novel anti-neoplastic agents and/or chemosensitizers that selectively sensitize cancer cells to platinum compounds. The present study describes the development of an amido-bridged nucleic acid (AmNA)-modified gapmer antisense oligonucleotide (ASO) targeting <i>MCM8</i>, called ASO 8–3419. In vitro, ASO 8–3419 inhibited MCM8 expression in several human cell lines and selectively sensitized cancer cells to cisplatin. Moreover, ASO 8–3419 modestly suppressed the growth of several cancer cell lines whose proliferation has been reported to depend on MCM8. In vivo, ASO 8–3419 inhibited the expression of MCM8 in xenografted tumors of colon cancer-derived HCT116 cells in nude mice and increased tumor sensitivity to cisplatin with minimal toxicity. These findings suggest that AmNA-modified, MCM8-specific ASOs hold promise as novel anti-cancer agents.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 5","pages":"1405-1416"},"PeriodicalIF":4.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651497","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":"LTF as a Potential Predictive Biomarker for Durable Benefit From First-Line Chemo-Immunotherapy in Small Cell Lung Cancer","authors":"Shimo Shen,&nbsp;Yili Wu,&nbsp;Zhuowei Shao,&nbsp;You Li,&nbsp;Di Peng,&nbsp;Bing Li,&nbsp;Zhou Zhang,&nbsp;Shibo Wu","doi":"10.1111/cas.70049","DOIUrl":"10.1111/cas.70049","url":null,"abstract":"<p>At present, only a limited fraction of patients with extensive-stage small cell lung cancer (ES-SCLC) achieve a sustained response to immune checkpoint blockade (ICB) therapy. The factors that drive therapeutic efficacy remain poorly delineated, and the field is devoid of reliable predictive biomarkers to guide personalized treatment decisions. Therefore, we conducted RNA sequencing of tumor samples from 21 patients prior to treatment to identify expression patterns associated with lasting benefit and used weighted gene co-expression network analysis (WGCNA) to identify key genes associated with favorable outcomes of chemotherapeutic immunotherapy. Multiplex immunofluorescence (mIF) quantification and reanalysis of publicly available datasets were used to validate the hub gene's association with the immune microenvironment and immunotherapy efficacy. The functional significance of the hub gene was further investigated in cellular models. We found that the durable clinical benefit (DCB) group exhibited significantly elevated levels of inflammation and interferon response compared to the no-durable benefit (NDB) group, alongside a notably lower proportion of Tregs and distinct metabolic features. Lactotransferrin (LTF) was identified as a hub gene associated with durable therapeutic benefits in chemo-immunotherapy. By further analysis, we proved that LTF acts as a tumor suppressor in small cell lung cancer, impacting cell proliferation, migration, and invasiveness. It also inhibits lipid metabolism in these cells. Elevated LTF expression is linked to better chemo-immunotherapy outcomes, suggesting its potential as a predictive biomarker for first-line treatment response in ES-SCLC.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 6","pages":"1522-1536"},"PeriodicalIF":4.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651502","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":"Claudin-11 Enhances Invasive and Metastatic Abilities of Small-Cell Lung Cancer Through MT1-MMP Activation","authors":"Shuichi Sakamoto,&nbsp;Hiroyuki Inoue,&nbsp;Takahisa Takino,&nbsp;Yasuko Kohda,&nbsp;Junjiro Yoshida,&nbsp;Shunichi Ohba,&nbsp;Ihomi Usami,&nbsp;Takeshi Suzuki,&nbsp;Manabu Kawada,&nbsp;Masanori Hatakeyama","doi":"10.1111/cas.70038","DOIUrl":"10.1111/cas.70038","url":null,"abstract":"<p>Small-cell lung cancer (SCLC) is an aggressive tumor characterized by the frequent development of distant metastases. This study aimed to explore the mechanism of SCLC metastasis using an originally developed orthotopic transplantation model with DMS273 cells. An analysis of G3H cells, a highly metastatic subline of DMS273 cells, revealed that claudin-11 promotes the invasive and metastatic ability of the cells. Further analysis revealed that membrane type 1-matrix metalloproteinase (MT1-MMP), which degrades a wide range of extracellular matrix components, was coprecipitated with claudin-11. Gelatin zymography revealed that claudin-11 enhanced MT1-MMP activity, and <i>MT1-MMP</i> silencing suppressed the invasive and metastatic ability of G3H cells. Moreover, in <i>MT1-MMP</i> silencing DMS273 cells, the enhancement of invasion and metastatic potential induced by <i>CLDN11</i> overexpression was abolished. These results demonstrate that claudin-11 enhances the invasive capacity of the cells by activating MT1-MMP, which promotes metastatic formation in the orthotopic transplantation model. Additionally, claudin-11 expression was detected in SCLC tumor samples, and higher expression of <i>CLDN11</i> correlated with poor prognosis in patients with SCLC. These findings suggest that the claudin-11/MT1-MMP axis plays an important role in SCLC pathogenesis.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 6","pages":"1773-1784"},"PeriodicalIF":4.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626374","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":"STAB1 Promotes Acute Myeloid Leukemia Progression by Activating the IKK/NF-κB Pathway and Increasing M2 Macrophage Polarization","authors":"Jiaxiu Yin,&nbsp;Jing Luo,&nbsp;Lan Wang,&nbsp;Lanxiang Liu,&nbsp;Lin Liu","doi":"10.1111/cas.70044","DOIUrl":"10.1111/cas.70044","url":null,"abstract":"<p>As a multifunctional scavenger receptor, stabilin-1 (STAB1) has been identified to induce chronic inflammation and promote cancer progression. Although in silico studies from multiple data sets showed that STAB1 might facilitate the progression of acute myeloid leukemia (AML) and drug resistance, the real impacts of STAB1 expression on AML patients and the detailed mechanisms remain unclear. Herein, we found that a higher expression of STAB1 is associated with a worse prognosis in AML patients. Subsequent in vitro experiments demonstrated that STAB1 knockdown suppressed proliferation and promoted apoptosis through regulating the IKK/NF-κB pathway in human AML cell lines HEL and NB4. In addition, in vivo studies showed that STAB1 silencing prolonged survival, reduced proliferation, and inhibited aggressiveness of AML cells in xenograft mouse models. Moreover, we investigated the impact of STAB1 expression in AML cells on macrophage differentiation and found that co-culture of macrophages with conditioned medium from STAB1-knockdown AML cells reduced M2 polarization of macrophages. Taken together, our study suggests that STAB1 promotes growth and aggressiveness of AML cells through activating the IKK/NF-κB pathway while also regulating M2 macrophage polarization within the chronic inflammatory environment. Therefore, targeting STAB1 could be a potential therapeutic strategy for treating AML.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 6","pages":"1508-1521"},"PeriodicalIF":4.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626496","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}