Cancer gene therapy最新文献_第10页

m6A epitranscriptomic regulation of KRAS by METTL3 promotes EMT and stromal remodeling through TGF-β/SMAD signaling in cervical cancer METTL3对KRAS的m6A表转录组调控通过TGF-β/SMAD信号在宫颈癌中促进EMT和间质重塑。

IF 5 3区医学

Cancer gene therapy Pub Date : 2026-01-03 DOI: 10.1038/s41417-025-00993-7

Yangmei Gong, Jie Wu, Yi Hu

引用次数: 0

The role of hsa_circ_0000520 in breast cancer progression: insights into the miR-542-3p/TMBIM6 regulatory axis hsa_circ_0000520在乳腺癌进展中的作用：对miR-542-3p/TMBIM6调控轴的见解

IF 6.4 3区医学

Cancer gene therapy Pub Date : 2025-12-18 DOI: 10.1038/s41417-025-00997-3

Feng Wang, RenCheng Sun, BaoKai Wang, GengBao Qu

{"title":"The role of hsa_circ_0000520 in breast cancer progression: insights into the miR-542-3p/TMBIM6 regulatory axis","authors":"Feng Wang, RenCheng Sun, BaoKai Wang, GengBao Qu","doi":"10.1038/s41417-025-00997-3","DOIUrl":"10.1038/s41417-025-00997-3","url":null,"abstract":"This work evaluated the action of hsa_circ_0000520 in breast cancer (BC) progression through miR-542-3p/TMBIM6 axis. Clinical specimens were harvested from BC patients, in which hsa_circ_0000520 expression was determined. BT-549 cells were taken for transfection to intervene gene expression correspondingly, after which cellular proliferative, invasive, migratory, and apoptotic activities were monitored. As well, under different treatment, the changes in relevant indicators were observed. A tumor model was established in mice to examine the action of hsa_circ_0000520. Mechanistic analysis using RIP and lufiferase reporter assay were conducted to verify the interaction between miR-542-3p and hsa_circ_0000520 or TMBIM6. hsa_circ_0000520 was elevated in its expression in BC tissues. hsa_circ_0000520 knockdown exerted an anti-tumor property to fight against cellular malignant phenotypes in vitro, as well as tumor development in vivo. hsa_circ_0000520, through an absorption effect, regulated miR-542-3p, thereby targeting TMBIM6. miR-542-3p upregulation or TMBIM6 downregulation counter-balanced the pro-tumor effects of hsa_circ_0000520 overexpression. hsa_circ_0000520 promotes BC proliferation and metastasis through miR-542-3p-targeted TMBIM6.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"33 6","pages":"708-717"},"PeriodicalIF":6.4,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NRAV promotes HCC stemness via the m6A-regulated let-7c-5p/LIN28B axis NRAV通过m6a调控的let-7c-5p/LIN28B轴促进HCC的发生。

IF 5 3区医学

Cancer gene therapy Pub Date : 2025-12-12 DOI: 10.1038/s41417-025-00995-5

Yuhang Chen, Suoyi Dai, Liping Zhuang, Wenxun Cai, Hao Chen, Jiangang Zhao, Fenglin Zhang, Lianyu Chen, Chien-Shan Cheng

{"title":"NRAV promotes HCC stemness via the m6A-regulated let-7c-5p/LIN28B axis","authors":"Yuhang Chen, Suoyi Dai, Liping Zhuang, Wenxun Cai, Hao Chen, Jiangang Zhao, Fenglin Zhang, Lianyu Chen, Chien-Shan Cheng","doi":"10.1038/s41417-025-00995-5","DOIUrl":"10.1038/s41417-025-00995-5","url":null,"abstract":"Long non-coding RNAs (lncRNAs) plays critical roles in hepatocellular carcinoma (HCC), but their post-transcriptional regulation via N6-methyladenosine (m6A) remains poorly understood. Here, we identify NRAV as an m6A-modified lncRNA that promotes HCC stemness through a defined molecular axis. Integrating bioinformatics analysis of TCGA data with in vitro and in vivo validation, we demonstrated that NRAV is significantly overexpressed in HCC and associated with poor prognosis. Mechanistically, NRAV acts as a competing endogenous RNA (ceRNA), sequestering hsa-let-7c-5p and preventing it from downregulating LIN28B, a key stemness factor. This leads to increased LIN28B protein levels and enhanced expression of cancer stem cell markers. MeRIP-qPCR and site-directed mutagenesis experiments confirm that m6A modification of NRAV is crucial for its function. In animal models and clinical tissues, NRAV expression correlates with disease progression and CSC marker accumulation. Our findings uncover a novel NRAV-let-7c-5p-LIN28B axis that links m6A modification to CSC maintenance in HCC, highlighting a potential therapeutic target for disrupting stemness pathways in liver cancer.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"33 2","pages":"171-185"},"PeriodicalIF":5.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41417-025-00995-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pleiotropic effects of all-trans retinoic acid in attenuating the hallmarks of colorectal cancer- challenges and scope of differentiation therapy 全反式维甲酸在减轻结直肠癌特征中的多效作用-分化治疗的挑战和范围。

IF 5 3区医学

Cancer gene therapy Pub Date : 2025-12-10 DOI: 10.1038/s41417-025-00996-4

Antony Anista Michael, Pavithra Balakrishnan, Priyadharshini Tamizhmani, Kishore Thirunavukarasu, Selvakumar Subramaniam, Thirunavukkarasu Velusamy

{"title":"Pleiotropic effects of all-trans retinoic acid in attenuating the hallmarks of colorectal cancer- challenges and scope of differentiation therapy","authors":"Antony Anista Michael, Pavithra Balakrishnan, Priyadharshini Tamizhmani, Kishore Thirunavukarasu, Selvakumar Subramaniam, Thirunavukkarasu Velusamy","doi":"10.1038/s41417-025-00996-4","DOIUrl":"10.1038/s41417-025-00996-4","url":null,"abstract":"Colorectal Cancer (CRC) is a heterogenous malignancy, attributed by a vast array of mutations that govern the adenoma-carcinoma sequence. The underlying molecular mechanism of CRC recurrence is diverse and complex, in which cancer stem cells (CSCs) remain a major determinant of therapy discontinuation and refractoriness. In contrast to reigning cytotoxic therapies in abolishing cancer cells, leveraging the cytodifferentiation approach offers an effective modality while sparing normal cells. The concept of differentiation therapy fosters from the notion that such cancer stem cells can be either reverted back to their lineage or terminally differentiated cancer cells upon exposure to differentiation inducing agents like All-trans retinoic acid (ATRA). Beyond driving cellular differentiation, ATRA mediates other cellular processes like cell cycle arrest, apoptosis, and abrogates metabolic plasticity, EMT and angiogenesis in cancer cells. These pleiotropic effects of ATRA in modulating the typical hallmarks of cancer and its therapeutic limitations are being studied since 1900s. Despite this, its mode of action and factors impeding its therapeutic effects have not been elucidated in detail and thus remains obscure. However, over the years, various molecular signatures and pathways implicated in the therapeutic effects of ATRA has been unravelled in pieces. In an attempt towards a better picture, the current review aims to highlight the molecular mechanism of ATRA in attenuating the hallmarks of CRC and the factors affecting its therapeutic efficacy from a holistic perspective.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"33 2","pages":"261-275"},"PeriodicalIF":5.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The legacy of a humble scientist: Edoardo Alesse, MD, PhD (1958–2025) 一个卑微的科学家的遗产：爱德华多·阿莱斯，医学博士，博士（1958-2025）。

IF 5 3区医学

Cancer gene therapy Pub Date : 2025-12-07 DOI: 10.1038/s41417-025-00994-6

Salvatore Papa, Concetta Bubici

引用次数: 0

PRDX1 depletion predisposes to ferroptosis through inhibiting the cAMP pathway in B-cell acute lymphoblastic leukemia 在b细胞急性淋巴细胞白血病中，PRDX1基因缺失通过抑制cAMP通路导致铁凋亡。

IF 6.4 3区医学

Cancer gene therapy Pub Date : 2025-12-05 DOI: 10.1038/s41417-025-00992-8

FangFang Zhong, Yan Zeng, Jing Liu, Qulian Guo, Ping Wen

{"title":"PRDX1 depletion predisposes to ferroptosis through inhibiting the cAMP pathway in B-cell acute lymphoblastic leukemia","authors":"FangFang Zhong, Yan Zeng, Jing Liu, Qulian Guo, Ping Wen","doi":"10.1038/s41417-025-00992-8","DOIUrl":"10.1038/s41417-025-00992-8","url":null,"abstract":"B-cell acute lymphoblastic leukemia (B-ALL) is a hematologic malignancy commonly found in pediatric patients. This study aims to screen hub genes in B-ALL and elucidate the role of peroxiredoxin 1 (PRDX1) in the modulation of ferroptosis. Bioinformatics analyses were conducted to identify pivotal genes in the GSE17703 and GSE48558 datasets. The biological effects of PRDX1 deletion in B-ALL cells and the xenograft tumor were evaluated using a series of functional assays. Ferroptosis was induced in B-ALL cells using erastin. Transcriptome sequencing was performed on Nalm-6 cells before and after PRDX1 knockdown. Forskolin was employed to explore the role of PRDX1 in the cyclic adenosine monophosphate (cAMP) pathway. Four pivotal genes were identified, with two genes upregulated and two downregulated. Depletion of PRDX1 suppressed the proliferative, migratory, and invasive abilities of B-ALL cells, whereas PRDX1 overexpression exerted the opposite effects. PRDX1 silencing promoted erastin-induced ferroptosis, including elevated levels of COX2, ACSL4, ferrous ions, ROS, and MDA, while reducing GPX4, GSH, and SOD levels. PRDX1 knockdown further reduced the viability of B-ALL cells treated with the ferroptosis activator ML210, and treatment with the ferroptosis inhibitor liproxstatin-1 significantly reversed the suppressive effect of PRDX1 knockdown on xenograft tumor growth. Mechanically, PRDX1 deletion triggered ferroptosis in B-ALL cells by inhibiting the cAMP pathway. PRDX1 deficiency modulates ferroptosis in B-ALL cells by blocking the cAMP pathway, which offer a novel perspective on the pathogenesis of B-ALL.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"33 5","pages":"505-518"},"PeriodicalIF":6.4,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41417-025-00992-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

AP-1 promotes oncogenic transcription in lung cancer cells by bridging promoter-enhancer interactions AP-1通过桥接启动子-增强子相互作用促进肺癌细胞的致癌转录。

IF 5 3区医学

Cancer gene therapy Pub Date : 2025-12-03 DOI: 10.1038/s41417-025-00974-w

Xianglong Tan, Michael Kroneberg, Fei Sun, Kevin Avelar Diaz, Alisha Flora, Michael F. Carey

{"title":"AP-1 promotes oncogenic transcription in lung cancer cells by bridging promoter-enhancer interactions","authors":"Xianglong Tan, Michael Kroneberg, Fei Sun, Kevin Avelar Diaz, Alisha Flora, Michael F. Carey","doi":"10.1038/s41417-025-00974-w","DOIUrl":"10.1038/s41417-025-00974-w","url":null,"abstract":"Mechanistic understanding of how transcription factors drive oncogene expression in lung cancer remains limited. Here, we utilized a cancer cell line-guided, multi-omic approach integrating promoter-capture Hi-C (pcHiC), ATAC-seq, ChIP-seq, and transcriptomics to identify epigenomic and 3D genomic alterations associated with oncogenes in non-small cell lung cancer (NSCLC) patients from The Cancer Genome Atlas (TCGA). Our cancer cell line accurately recapitulates key transcriptomic and epigenomic alterations observed in NSCLC patient samples. Comprehensive multi-omic analyses revealed aberrant activation of the bZIP family oncogenic transcription factor AP-1 in lung cancer cells. Clinically, AP-1 activation significantly correlated with patient outcomes in TCGA data, where elevated AP-1 expression levels were associated with increased mortality in lung squamous cell carcinoma patients. UMAP projections further demonstrated that AP-1-driven oncogene expression is specifically enriched in NSCLC patients exhibiting high AP-1 expression levels. Mechanistically, we observed enhanced promoter-enhancer interactions mediated by AP-1 at multiple upregulated oncogenes. Pharmacological inhibition of AP-1, either directly via AP-1 inhibitor SR11302 or indirectly through its upstream JNK pathway inhibition via SP600125, suppressed AP-1-driven oncogenic transcription and reduced promoter-enhancer looping. Our findings highlight the pivotal role of AP-1 in oncogenic transcription in NSCLC, revealing that transcription factors enhance oncogene expression by facilitating promoter-enhancer interactions.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"33 3","pages":"301-313"},"PeriodicalIF":5.0,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41417-025-00974-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

p53-armed oncolytic adenovirus induces apoptosis in pancreatic cancer-associated stellate cells via macropinocytosis p53武装溶瘤腺病毒通过巨噬细胞作用诱导胰腺癌相关星状细胞凋亡。

IF 5 3区医学

Cancer gene therapy Pub Date : 2025-11-28 DOI: 10.1038/s41417-025-00989-3

Takeyoshi Nishiyama, Hiroshi Tazawa, Yasuo Nagai, Ryohei Shoji, Yoshinori Kajiwara, Naoyuki Hashimoto, Yosuke Takahashi, Satoru Kikuchi, Shinji Kuroda, Toshiaki Ohara, Kazuhiro Noma, Ryuichi Yoshida, Yuzo Umeda, Hiroyoshi Y. Tanaka, Mitsunobu R. Kano, Atsushi Masamune, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara

{"title":"p53-armed oncolytic adenovirus induces apoptosis in pancreatic cancer-associated stellate cells via macropinocytosis","authors":"Takeyoshi Nishiyama, Hiroshi Tazawa, Yasuo Nagai, Ryohei Shoji, Yoshinori Kajiwara, Naoyuki Hashimoto, Yosuke Takahashi, Satoru Kikuchi, Shinji Kuroda, Toshiaki Ohara, Kazuhiro Noma, Ryuichi Yoshida, Yuzo Umeda, Hiroyoshi Y. Tanaka, Mitsunobu R. Kano, Atsushi Masamune, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara","doi":"10.1038/s41417-025-00989-3","DOIUrl":"10.1038/s41417-025-00989-3","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC)-associated pancreatic stellate cells (PSCs) promote PDAC tumor progression. Notably, PDAC tumors display enhanced macropinocytosis, resulting in enhanced uptake of extracellular particles, including nutrients and viruses. We previously demonstrated the therapeutic potential of telomerase-specific oncolytic adenoviruses OBP-301 and p53-armed OBP-702 against human PDAC cells. However, it remains unclear whether macropinocytosis promotes the virus sensitivity of PDAC-associated PSCs. Here, we show that PSCs activated by human PDAC cells (Panc-1 and BxPC-3) exhibit enhanced sensitivity to wild-type and oncolytic adenoviruses via enhanced macropinocytosis. The virus sensitivity of PSCs was analyzed for the infectivity, replication, and cytopathic activity of wild-type and oncolytic adenoviruses. PDAC-associated PSCs were more sensitive to wild-type and oncolytic adenoviruses than were control PSCs; this sensitivity was mediated by activation of macropinocytosis. In three-dimensional (3D) culture models, p53-armed OBP-702 decreased the viability of PDAC-associated PSCs more strongly than did non-armed OBP-301, reflecting induction of p53-mediated apoptosis. Co-inoculation of PSCs enhanced the growth of PDAC tumors, an effect that was attenuated by OBP-702-mediated p53 activation in the tumor stroma. Our results suggest that p53-armed oncolytic adenovirus OBP-702 eliminates PDAC-associated PSCs via enhancement of macropinocytosis-mediated virus entry and induction of p53-mediated apoptosis.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"33 2","pages":"223-235"},"PeriodicalIF":5.0,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41417-025-00989-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145629438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CSF1-CSF1R signaling mediates tumor cell-macrophage crosstalk and prognosis in ccRCC CSF1-CSF1R信号在ccRCC中介导肿瘤细胞-巨噬细胞串扰和预后。

IF 6.4 3区医学

Cancer gene therapy Pub Date : 2025-11-27 DOI: 10.1038/s41417-025-00983-9

Xing Li, Yanjun Li, Lei Zhang, Libin Zhou, Huimin Long

{"title":"CSF1-CSF1R signaling mediates tumor cell-macrophage crosstalk and prognosis in ccRCC","authors":"Xing Li, Yanjun Li, Lei Zhang, Libin Zhou, Huimin Long","doi":"10.1038/s41417-025-00983-9","DOIUrl":"10.1038/s41417-025-00983-9","url":null,"abstract":"Clear cell renal cell carcinoma (ccRCC) is a common and aggressive kidney cancer with poor prognosis due to its frequent late-stage diagnosis and immunosuppressive tumor microenvironment (TME). While ccRCC is responsive to immunotherapies, treatment resistance remains a major challenge, underscoring the need for new therapeutic targets. We performed integrated single-cell and bulk transcriptomic analysis of ccRCC and normal kidney tissues to characterize the immune landscape and identify key ligand–receptor interactions within the TME. Gene expression and survival data were analyzed using public datasets. Functional validation was conducted using a ccRCC xenograft mouse model treated with the CSF1R inhibitor Sotuletinib. Single-cell analysis revealed that enhanced communication between M2-like macrophages and malignant epithelial cells in ccRCC, with the CSF1-CSF1R signaling axis playing a central role. Elevated expression of CSF1 and CSF1R correlated with poor patient prognosis and increased macrophage infiltration. In vivo inhibition of CSF1R reduced tumor growth, decreased Ki67+ cell proliferation, and suppressed CD163+ M2 macrophage polarization. This study suggests a potential role of CSF1-CSF1R-mediated macrophage-epithelial crosstalk in promoting immunosuppressive TME and tumor progression in ccRCC. Importantly, CellChat-based predictions represent potential, rather than definitive, ligand–receptor interactions, and thus require further mechanistic validation. Targeting CSF1R may offer a promising strategy to modulate the immune landscape and improve therapeutic outcomes in ccRCC.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"33 4","pages":"367-377"},"PeriodicalIF":6.4,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41417-025-00983-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145629410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Construction of the cancer cell continuum reveals hybrid EMT state driving lung adenocarcinoma aggression 癌细胞连续体的构建揭示了混合EMT状态驱动肺腺癌的侵袭。

IF 5 3区医学

Cancer gene therapy Pub Date : 2025-11-25 DOI: 10.1038/s41417-025-00991-9

Qiuhao Qu, Yixin Ma, Chao Huang, Botao Fa, Zhenni Liu, Yuhan Li, Shigao Yang, Zhengtao Xiao

{"title":"Construction of the cancer cell continuum reveals hybrid EMT state driving lung adenocarcinoma aggression","authors":"Qiuhao Qu, Yixin Ma, Chao Huang, Botao Fa, Zhenni Liu, Yuhan Li, Shigao Yang, Zhengtao Xiao","doi":"10.1038/s41417-025-00991-9","DOIUrl":"10.1038/s41417-025-00991-9","url":null,"abstract":"The epithelial-to-mesenchymal transition (EMT) is a pivotal cellular process integral to metastasis. Emerging evidence indicates that EMT progresses through a continuum of cellular states, yet the intricate regulatory mechanisms underpinning this transition are not fully elucidated. This study aims to reconstruct the EMT spectrum in lung adenocarcinoma (LUAD) by integrating single-cell RNA sequencing data with advanced cell trajectory inference techniques. We identified five distinct EMT states across 16,310 malignant epithelial cells derived from 10 LUAD patients, encompassing epithelial, mesenchymal, and hybrid epithelial/mesenchymal (E/M) phenotypes. Notably, the hybrid E/M states exhibited the highest metastatic potential and were correlated with a poorer prognosis for patients. By modeling the EMT regulatory network, we evaluated the influence of transcription factor (TF) activation on network stability during cellular state transitions. We identified critical TFs, including TCF7, FOXA1, FOXA2, and SMAD7, which collectively regulate pathways such as TGF-β through both intrinsic EMT-related signaling and the modulation of tumor-associated macrophages. Furthermore, we developed a risk stratification model based on EMT continuum signatures, providing a novel tool for prognostic assessment. Our findings contribute to a comprehensive understanding of EMT-driven tumor evolution and open new avenues for prognostic stratification and targeted therapies in LUAD.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"33 2","pages":"186-197"},"PeriodicalIF":5.0,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145602516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0