Molecular Cancer最新文献

{"title":"SLAMF receptors: key regulators of tumor progression and emerging targets for cancer immunotherapy","authors":"Jia Li, Tao Fan, Di Wang, Chu Xiao, Ziqin Deng, Wenpeng Cai, Yu Ji, Chunxiang Li, Jie He","doi":"10.1186/s12943-025-02308-8","DOIUrl":"https://doi.org/10.1186/s12943-025-02308-8","url":null,"abstract":"The signaling lymphocytic activation molecule family (SLAMF) consists of nine distinct cell surface receptors predominantly expressed on immune cells, each characterized by unique structural features, expression patterns, downstream signaling pathways, and biological functions. These receptors play critical roles in modulating various immune cell activities within the tumor microenvironment, thereby shaping immune responses in cancer. Although accumulating evidence demonstrates their value as therapeutic targets for developing cancer immunotherapies, the full spectrum of SLAMF receptors in cancer remains incompletely understood. This review aims to provide a comprehensive overview of the molecular characteristics and immunomodulatory functions of each SLAMF receptor, underscoring their pivotal contributions to cancer progression. Furthermore, we also highlight their potential as promising targets for advancing cancer immunotherapeutic strategies. Finally, we discuss clinical trials evaluating the efficacy and safety of SLAMF receptor-based immunotherapies, emphasizing their translational relevance in the development of cancer treatments.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"16 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perioperative nivolumab and chemotherapy in locally advanced squamous cell carcinoma of the oesophagus: a randomized multicentre phase 2 study with circulating tumor DNA dynamics monitoring","authors":"Heng Jiao, Siyun Lin, Jianmin Gu, Dongxian Jiang, Peng Cui, Zhiliang Huang, Yong Fang, Hao Wang, Miao Lin, Han Tang, Tian Jiang, Guangyi Lin, Shaoyuan Zhang, Hao Yin, Fei Liang, Jingshu Wang, Xuning Fan, Fujun Qiu, Yang Yang, Zhigang Li, Bin Li, Jiaqing Xiang, Xuefeng Leng, Yongtao Han, Chengcheng Li, Luoyan Ai, Yingyong Hou, Guoqiang Wang, Zhihong Zhang, Shangli Cai, Tianshu Liu, Jun Yin, Lijie Tan","doi":"10.1186/s12943-025-02332-8","DOIUrl":"https://doi.org/10.1186/s12943-025-02332-8","url":null,"abstract":"Although neoadjuvant chemotherapy and immunotherapy show promise in treating oesophageal squamous cell carcinoma (OSCC), long-term survival data are limited. This randomized, multicenter phase 2 study evaluated the efficacy of perioperative Nivolumab with chemotherapy, followed by surgery and adjuvant immunotherapy, in patients with locally advanced resectable OSCC, and explored the prognostic role of circulating tumor DNA (ctDNA) status. In this trial, participants recruited from five centers were randomly assigned in a 2:1 ratio to receive either perioperative Nivolumab or a placebo in addition to chemotherapy (cisplatin and paclitaxel), followed by minimally invasive esophagectomy. For those who did not achieve a pathological complete response (pCR), adjuvant treatment with Nivolumab was administered. The main measure of success was the pCR rate, with secondary endpoints including the R0 resection rate, event-free survival, and overall survival. All outcomes and safety measures were assessed based on the intention-to-treat population. ctDNA levels were monitored as exploratory endpoints. Ninety patients were enrolled and randomized to Nivolumab or placebo plus chemotherapy. The pCR rate was slightly higher in the Nivolumab group (15%) compared to the control group (13.3%) (relative risk, 1.13; 95% CI, 0.38 to 3.36). No significant differences were observed in R0 resection rates (96.4% vs. 96.6%; P > 0.05). The median follow-up duration was 24.9 months (interquartile range: 22.8 to 26.7 months). Two-year event-free survival rates were 63.11% in the Nivolumab group versus 60.47% in the chemo group (hazard ratio, 0.97; 95% CI, 0.49 to 1.92). Two-year overall survival rates were 83.32% and 79.4%, respectively (hazard ratio, 0.82; 95% CI, 0.29 to 2.31). All participants were ctDNA positive at baseline, but post-treatment, 89% of the Nivolumab group and 62.5% of the placebo group turned ctDNA negative (P = 0.01). Those negative for ctDNA at all testing points showed significantly better disease-free survival (P < 0.001). Perioperative Nivolumab plus chemotherapy is a viable and safe option for systemically treating locally advanced resectable OSCC. Monitoring minimal residual disease through ctDNA could be potentially valuable for assessing the effectiveness of adjuvant therapy and for prognostic evaluation in a systemic manner. ClinicalTrials.gov registration NCT05213312.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"28 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissecting small cell carcinoma of the esophagus ecosystem by single-cell transcriptomic analysis","authors":"Hao-Xiang Wu, Yu-Kun Chen, Ying-Nan Wang, Jia-Ying Chen, Shu-Jing Xiang, Ying Jin, Zi-Xian Wang, Chun-Yu Huang, Lu-Ping Yang, Ye He, Wen-Long Guan, Long Bai, Yan-Xing Chen, Min Wang, Chao-Ye Wang, Run-Jie Huang, Yue Huang, Jin-Ling Zhang, Zhi-Da Lv, Si-Qi Yang, Rui-Hua Xu, Qi Zhao, Feng Wang","doi":"10.1186/s12943-025-02335-5","DOIUrl":"https://doi.org/10.1186/s12943-025-02335-5","url":null,"abstract":"Small cell carcinoma of the esophagus (SCCE) is an aggressive and rare neuroendocrine malignancy with poor prognosis. Here, we firstly performed single-cell transcriptional profiling derived from 10 SCCE patients, with normal esophageal mucosa, adjacent non-malignant tissue and tumors from esophageal squamous cell carcinoma (ESCC) as reference. We observed enrichment of activated regulatory T cells and an angiogenesis-induced niche existed in SCCE compared with ESCC, revealing an immune suppressive and vessel-induced tumor microenvironment (TME) in SCCE. Totally, we identified five TME ecotypes (EC1 ~ 5). Notably, EC1 was highly enriched in SCCE, associating with molecular subtyping and survival outcomes. To dissecting heterogeneity of epithelium in SCCE, we constructed eight transcriptional metaprograms (MPs) that underscored significant heterogeneity of SCCE. High expression of MP5 was linked to neuroendocrine phenotype and poor clinical survival. Collectively, these results, for the first time, systematically deciphered the TME and epithelial heterogeneity of SCCE and provided evidences that SCCE patients might benefit from anti-angiogenesis therapy.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"29 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Death-ision: the link between cellular resilience and cancer resistance to treatments","authors":"Gustavo Baldassarre, Ivana L. de la Serna, François M. Vallette","doi":"10.1186/s12943-025-02339-1","DOIUrl":"https://doi.org/10.1186/s12943-025-02339-1","url":null,"abstract":"One of the key challenges in defeating advanced tumors is the ability of cancer cells to evade the selective pressure imposed by chemotherapy, targeted therapies, immunotherapy and cellular therapies. Both genetic and epigenetic alterations contribute to the development of resistance, allowing cancer cells to survive initially effective treatments. In this narration, we explore how genetic and epigenetic regulatory mechanisms influence the state of tumor cells and their responsiveness to different therapeutic strategies. We further propose that an altered balance between cell growth and cell death is a fundamental driver of drug resistance. Cell death programs exist in various forms, shaped by cell type, triggering factors, and microenvironmental conditions. These processes are governed by temporal and spatial constraints and appear to be more heterogeneous than previously understood. To capture the intricate interplay between death-inducing signals and survival mechanisms, we introduce the concept of Death-ision. This framework highlights the dynamic nature of cell death regulation, determining whether specific cancer cell clones evade or succumb to therapy. Building on this understanding offers promising strategies to counteract resistant clones and enhance therapeutic efficacy. For instance, combining DNMT inhibitors with immune checkpoint blockade may counteract YAP1-driven resistance or the use of transcriptional CDK inhibitors could prevent or overcome chemotherapy resistance. Death-ision aims to provide a deeper understanding of the diversity and evolution of cell death programs, not only at diagnosis but also throughout disease progression and treatment adaptation.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"4 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiling triple-negative breast cancer-specific super-enhancers identifies high-risk mesenchymal development subtype and BETi-Targetable vulnerabilities","authors":"Qing-shan Chen, Rui-zhao Cai, Yan Wang, Ge-hao Liang, Kai-ming Zhang, Xiao-Yu Yang, Dong Yang, De-Chang Zhao, Xiao-Feng Zhu, Rong Deng, Jun Tang","doi":"10.1186/s12943-025-02342-6","DOIUrl":"https://doi.org/10.1186/s12943-025-02342-6","url":null,"abstract":"Super-enhancers (SEs) are critical regulators of tumorigenesis and represent promising targets for bromodomain and extra-terminal domain inhibitors (BETi). However, clinical studies across various solid tumors, including triple-negative breast cancer (TNBC), have demonstrated limited BETi efficacy. This study aims to investigate SE heterogeneity in TNBC and its influence on BETi effectiveness, with the goal of advancing BETi precision treatment strategies and enhancing therapeutic efficacy. We conducted a comprehensive analysis of H3K27ac ChIP-Seq data from TNBC cell lines and clinical samples, integrating multiple bulk RNA-Seq, scRNA-Seq, and stRNA-Seq datasets to characterize the SE landscape and heterogeneity in TNBC. Utilizing various bioinformatics algorithms, CERES scoring, and clinical prognostic data on transcription factors (TFs), we identified core transcriptional regulatory circuits (CRCs) composed of TNBC-specific SEs and master regulators, characterizing different TNBC subtypes. The biological significance of CRCs in these different TNBC subtypes and their influence on BETi sensitivity were evaluated using in vitro and in vivo models. Our findings revealed a distinct SE landscape in TNBC compared to non-TNBC and normal breast epithelium, allowing TNBC to be classified into distinct subtypes based on TNBC-specific SEs. Importantly, we identified a high-risk mesenchymal development subtype, validated across cell lines and transcriptomic analyses, primarily driven by a CRC consisting of the master regulator VAX2 and a TNBC-specific SE. This SE-VAX2 CRC is essential for sustaining the malignant traits of this subtype and increasing its sensitivity to BETi. Our research clarifies the heterogeneity of SEs in TNBC and identifies a high-risk mesenchymal development subtype driven by the SE-VAX2 CRC. The subtype shows more sensitivity to BETi, supporting its precision application in TNBC.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"26 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-glycosylation of PD-L1 modulates the efficacy of immune checkpoint blockades targeting PD-L1 and PD-1","authors":"Bar Kaufman, Muhammad Abu-Ahmad, Olga Radinsky, Eman Gharra, Tal Manko, Baisali Bhattacharya, Daniela Gologan, Nofar Erlichman, Tsipi Meshel, Yoav Nuta, Tomer Cooks, Moshe Elkabets, Adit Ben-Baruch, Angel Porgador","doi":"10.1186/s12943-025-02330-w","DOIUrl":"https://doi.org/10.1186/s12943-025-02330-w","url":null,"abstract":"The PD-L1/PD-1 pathway is crucial for immune regulation and has become a target in cancer immunotherapy. However, in order to improve patient selection for immune checkpoint blockade (ICB) therapies, better selection criteria are needed. This study explores how the N-glycosylation of PD-L1 affects its interaction with PD-1 and ICB efficacy, focusing on its four N-linked glycosylation sites: N35, N192, N200, and N219. Human PD-L1 glycosylation mutants—at each individual site or at all four sites together (Nx4)—were tested for their functional interaction with PD-1 using an artificial immune checkpoint reporter assay (IcAR-PD1). The blocking efficacy of anti-PD-L1 and anti-PD-1 antibodies was evaluated using human breast cancer cell lines (MDA-MB231 and MCF7), as well as A375 melanoma and A549 lung carcinoma cells expressing the glycosylation mutants. Results were validated through ex vivo activation and cytotoxicity assays using human CD8+ T cells. The binding of the PD-L1N35A mutant to PD-1 was not effectively blocked by anti-PD-L1 and anti-PD-1 ICBs. In contrast, high blocking efficacy of PD-L1 binding to PD-1 was obtained at minimal ICB concentrations when PD-L1 did not express any glycosylation site (PD-L1Nx4 mutant). The PD-L1N35A mutant produced elevated levels of PD-L1 as a soluble (sPD-L1) and extracellular vesicles (EV)-bound molecule; in contrast, the PD-L1Nx4 mutant had lower sPD-L1 and EV levels. PD-L1 glycosylation status influenced the ability of PD-L1 interactions with PD-1 to down-regulate T-cell activation and cytotoxicity, with the PD-L1N35A mutant showing the lowest levels of T cell functions and the PD-L1Nx4 mutant the highest. The N-glycosylation of PD-L1 at all four sites interferes with the ability of anti-PD-L1 and anti-PD-1 ICBs to block PD-L1 interactions with PD-1; in contrast, glycosylation at the N35 site enhances ICB blocking efficacy. These effects are connected to the ability of sPD-L1 to compete with ICB binding to PD-L1 or PD-1. Thus, assessing PD-L1 glycosylation, beyond expression levels, could improve patient stratification and outcomes.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"1 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the HER2-ELF3-KRAS axis: a novel therapeutic strategy for KRASG13D colorectal cancer.","authors":"Soo-Yeon Hwang,Yoojeong Seo,Seojeong Park,Seul-Ah Kim,Inhye Moon,Yi Liu,Seojeong Kim,Eun Seon Pak,Sehyun Jung,Hyeyoon Kim,Kyung-Hwa Jeon,Seung Hee Seo,Inyoung Sung,Heetak Lee,So-Yeon Park,Younghwa Na,Tae Il Kim,Youngjoo Kwon","doi":"10.1186/s12943-025-02343-5","DOIUrl":"https://doi.org/10.1186/s12943-025-02343-5","url":null,"abstract":"Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, with KRAS mutations playing a significant role in its tumorigenesis. Among the KRAS variants, the G13D mutation is associated with poor prognosis and distinctive biological behaviors. This study focuses on the role of HER2, a critical prognostic and predictive biomarker, in modulating the unique characteristics of KRASG13D-mutated CRCs. We identified a novel transcriptional regulatory network involving HER2, ELF3, and KRAS, with ELF3 acting as a key transcription factor (TF) that regulates KRAS expression under conditions of HER2 overexpression. Our findings reveal that this HER2-ELF3-KRAS axis is exclusively activated in KRASG13D, driving aggressive oncogenic features and conferring resistance to cetuximab (CTX) therapy. Through comprehensive analysis of gene expression profiles, we demonstrated that HER2 is a crucial therapeutic target specifically for KRASG13D CRCs. To explore this further, we introduced YK1, a small molecule inhibitor designed to disrupt the ELF3-MED23 interaction, leading to the transcriptional downregulation of HER2 and KRAS. This intervention significantly attenuated the HER2-ELF3-KRAS axis, sensitizing KRASG13D CRCs to CTX and reducing their tumorigenic potential by inhibiting the epithelial-to-mesenchymal transition process. Our study underscores the importance of HER2 as a key determinant in the unique biological characteristics of KRASG13D CRCs and highlights the therapeutic potential of targeting the HER2-ELF3-KRAS axis. By presenting YK1 as a novel pharmacological approach, we provide a promising strategy for developing tailored interventions for KRASG13D CRCs, contributing to the ongoing efforts in precision medicine for CRCs.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"125 1","pages":"139"},"PeriodicalIF":37.3,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive overview of ovarian cancer stem cells: correlation with high recurrence rate, underlying mechanisms, and therapeutic opportunities.","authors":"Hadi Alizadeh,Parastoo Akbarabadi,Alireza Dadfar,Mohammad Reza Tareh,Bahram Soltani","doi":"10.1186/s12943-025-02345-3","DOIUrl":"https://doi.org/10.1186/s12943-025-02345-3","url":null,"abstract":"Ovarian cancer is one of the most lethal gynecological malignancies, with a recurrence rate of 70-80%, particularly in patients diagnosed at advanced stages (stage III or IV), where the five-year survival rate falls below 30%. A key driver of this recurrence is the presence of cancer stem cells (CSCs), which exhibit resistance to chemotherapy and possess the capacity for self-renewal, plasticity, and tumor regeneration. The tumor microenvironment (TME) plays a crucial role in maintaining ovarian cancer stem cells (OCSCs) by providing nutrient and oxygen gradients, extracellular matrix (ECM) interactions, immune cell modulation, and support from cancer-associated fibroblasts (CAFs). CAFs secrete growth factors, cytokines, and ECM components that create a pro-tumorigenic niche, promoting CSC maintenance, invasion, and chemoresistance. Additionally, dysregulation of critical signaling pathways, including WNT, NOTCH, PI3K/AKT/mTOR, TGF-β, JAK/STAT, Hedgehog, NF-κB, and Hippo, supports CSC stemness, plasticity, maintenance, and adaptability, thereby increasing their survival and progression. Numerous inhibitors targeting these pathways have shown promise in preclinical studies. This review discusses the molecular mechanisms underlying CSC-mediated recurrence in ovarian cancer and highlights emerging therapeutic strategies. Particular emphasis is placed on the potential of combination therapies involving routine platinum or taxane based regimens with OCSC inhibitors to overcome chemoresistance, reduce recurrence rates, and improve survival outcomes for patients with advanced-stage ovarian cancer.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"13 1","pages":"135"},"PeriodicalIF":37.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: SPOP‑mediated ubiquitination and degradation of PDK1 suppresses AKT kinase activity and oncogenic functions","authors":"Qiwei Jiang, Nana Zheng, Lang Bu, Xiaomei Zhang, Xiaoling Zhang, Yuanzhong Wu, Yaqing Su, Lei Wang, Xiaomin Zhang, Shancheng Ren, Xiangpeng Dai, Depei Wu, Wei Xie, Wenyi Wei, Yasheng Zhu, Jianping Guo","doi":"10.1186/s12943-025-02347-1","DOIUrl":"https://doi.org/10.1186/s12943-025-02347-1","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Correction&lt;/b&gt;&lt;b&gt;: &lt;/b&gt;&lt;b&gt;Mol Cancer 20, 100 (2021)&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;https://doi.org/10.1186/s12943-021-01397-5&lt;/b&gt;&lt;/p&gt;&lt;br/&gt;&lt;p&gt;Following publication of the original article [1], the authors identified the tubulin band of Figure 2C and 4M was duplicated used. They sincerely apologize for the inadvertent duplication during data arrangement. Here, they provide the original data to clarify that these tubulin bands were run on the same gel. However, when excising the bands, the wrong side was mistakenly used. The original raw data for all figures have been properly archived and are readily available for verification. Now they have corrected this error and provided the updated Figure 4. The error does not affect the conclusion. The updated Figure 4 is provided below.&lt;/p&gt;&lt;p&gt;Updated Fig. 4&lt;/p&gt;&lt;figure&gt;&lt;figcaption&gt;&lt;b data-test=\"figure-caption-text\"&gt;Fig. 4&lt;/b&gt;&lt;/figcaption&gt;&lt;picture&gt;&lt;source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02347-1/MediaObjects/12943_2025_2347_Fig1_HTML.png?as=webp\" type=\"image/webp\"/&gt;&lt;img alt=\"figure 1\" aria-describedby=\"Fig1\" height=\"639\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02347-1/MediaObjects/12943_2025_2347_Fig1_HTML.png\" width=\"685\"/&gt;&lt;/picture&gt;&lt;p&gt;CK1/GSK3-mediated PDK1 phosphorylation promotes SPOP interaction with and ubiquitination of PDK1&lt;/p&gt;&lt;span&gt;Full size image&lt;/span&gt;&lt;svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"&gt;&lt;use xlink:href=\"#icon-eds-i-chevron-right-small\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;/use&gt;&lt;/svg&gt;&lt;/figure&gt;&lt;ol data-track-component=\"outbound reference\" data-track-context=\"references section\"&gt;&lt;li data-counter=\"1.\"&gt;&lt;p&gt;Jiang Q, Zheng N, Bu L, et al. SPOP-mediated ubiquitination and degradation of PDK1 suppresses AKT kinase activity and oncogenic functions. Mol Cancer. 2021;20:100. https://doi.org/10.1186/s12943-021-01397-5.&lt;/p&gt;&lt;p&gt;Article CAS PubMed PubMed Central Google Scholar &lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;p&gt;Download references&lt;svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"&gt;&lt;use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;/use&gt;&lt;/svg&gt;&lt;/p&gt;&lt;span&gt;Author notes&lt;/span&gt;&lt;ol&gt;&lt;li&gt;&lt;p&gt;Qiwei Jiang, Nana Zheng and Lang Bu contributed equally to this work.&lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;h3&gt;Authors and Affiliations&lt;/h3&gt;&lt;ol&gt;&lt;li&gt;&lt;p&gt;Institute of Precision Medicine, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510275, Guangdong, China&lt;/p&gt;&lt;p&gt;Qiwei Jiang, Lang Bu, Xiaomei Zhang, Yaqing Su, Lei Wang, Wei Xie &amp; Jianping Guo&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China&lt;/p&gt;&lt;p&gt;Nana Zheng &amp; Depei Wu&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, Institute of Immunology, The First Hospital, Jilin University, Jilin, Changchun, China&lt;/p&gt;&lt;p&gt;Xiaoling Zh","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"16 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein lipidation in the tumor microenvironment: enzymology, signaling pathways, and therapeutics","authors":"Mengke Xu, Bo Xu","doi":"10.1186/s12943-025-02309-7","DOIUrl":"https://doi.org/10.1186/s12943-025-02309-7","url":null,"abstract":"Protein lipidation is a pivotal post-translational modification that increases protein hydrophobicity and influences their function, localization, and interaction network. Emerging evidence has shown significant roles of lipidation in the tumor microenvironment (TME). However, a comprehensive review of this topic is lacking. In this review, we present an integrated and in-depth literature review of protein lipidation in the context of the TME. Specifically, we focus on three major lipidation modifications: S-prenylation, S-palmitoylation, and N-myristoylation. We emphasize how these modifications affect oncogenic signaling pathways and the complex interplay between tumor cells and the surrounding stromal and immune cells. Furthermore, we explore the therapeutic potential of targeting lipidation mechanisms in cancer treatment and discuss prospects for developing novel anticancer strategies that disrupt lipidation-dependent signaling pathways. By bridging protein lipidation with the dynamics of the TME, our review provides novel insights into the complex relationship between them that drives tumor initiation and progression.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"62 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}