Cancer research最新文献_第9页

HDAC Inhibition Increases CXCL12 Secretion to Recruit Natural Killer Cells in Peripheral T-cell Lymphoma. HDAC 抑制可增加 CXCL12 分泌，从而招募外周 T 细胞淋巴瘤中的自然杀伤细胞。

IF 12.5 1区医学

Cancer research Pub Date : 2024-08-01 DOI: 10.1158/0008-5472.CAN-23-3250

Jiayan Zhu, Feng Wang, Lining Wang, Bo Dai, Guilin Xu, Luyao Zhao, Huimin Jiang, Wenhui Gao, Tingting Zhang, Chenxi Zhao, Yun-Xuan Li, Jiong Hu, Ke Li

{"title":"HDAC Inhibition Increases CXCL12 Secretion to Recruit Natural Killer Cells in Peripheral T-cell Lymphoma.","authors":"Jiayan Zhu, Feng Wang, Lining Wang, Bo Dai, Guilin Xu, Luyao Zhao, Huimin Jiang, Wenhui Gao, Tingting Zhang, Chenxi Zhao, Yun-Xuan Li, Jiong Hu, Ke Li","doi":"10.1158/0008-5472.CAN-23-3250","DOIUrl":"10.1158/0008-5472.CAN-23-3250","url":null,"abstract":"Peripheral T-cell lymphoma (PTCL) is a heterogeneous and aggressive disease with a poor prognosis. Histone deacetylase (HDAC) inhibitors have shown inhibitory effects on PTCL. A better understanding of the therapeutic mechanism underlying the effects of HDAC inhibitors could help improve treatment strategies. Herein, we found that high expression of HDAC3 is associated with poor prognosis in PTCL. HDAC3 inhibition suppressed lymphoma growth in immunocompetent mice but not in immunodeficient mice. HDAC3 deletion delayed the progression of lymphoma, reduced the lymphoma burden in the thymus, spleen, and lymph nodes, and prolonged the survival of mice bearing N-methyl-N-nitrosourea-induced lymphoma. Furthermore, inhibiting HDAC3 promoted the infiltration and enhanced the function of natural killer (NK) cells. Mechanistically, HDAC3 mediated ATF3 deacetylation, enhancing its transcriptional inhibitory activity. Targeting HDAC3 enhanced CXCL12 secretion through an ATF3-dependent pathway to stimulate NK-cell recruitment and activation. Finally, HDAC3 suppression improved the response of PTCL to conventional chemotherapy. Collectively, this study provides insights into the mechanism by which HDAC3 regulates ATF3 activity and CXCL12 secretion, leading to immune infiltration and lymphoma suppression. Combining HDAC3 inhibitors with chemotherapy may be a promising strategy for treating PTCL. Significance: Targeting HDAC3 suppresses progression of T-cell lymphoma by activating ATF3 to induce secretion of CXCL12 and promote infiltration of NK cells, providing an immunostimulatory approach for treating T-cell lymphoma patients.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140891162","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}

引用次数: 0

Dietary Commensal Wrestles Iron from Tumor Microenvironment to Activate Antitumoral Macrophages. 膳食共生菌从肿瘤微环境中夺取铁元素，激活抗肿瘤巨噬细胞。

IF 12.5 1区医学

Cancer research Pub Date : 2024-08-01 DOI: 10.1158/0008-5472.CAN-24-1833

Amanda H Lee, Simran K Randhawa, Marlies Meisel

{"title":"Dietary Commensal Wrestles Iron from Tumor Microenvironment to Activate Antitumoral Macrophages.","authors":"Amanda H Lee, Simran K Randhawa, Marlies Meisel","doi":"10.1158/0008-5472.CAN-24-1833","DOIUrl":"10.1158/0008-5472.CAN-24-1833","url":null,"abstract":"The microbiome dictates the response to cancer immunotherapy efficacy. However, the mechanisms of how the microbiota impacts therapy efficacy remain poorly understood. In a recent issue of Nature Immunology, Sharma and colleagues elucidate a multifaceted, macrophage-driven mechanism exerted by a specific strain of fermented food commensal plantarum strain IMB19, LpIMB19. LpIMB19 activates tumor macrophages, resulting in the enhancement of cytotoxic cluster differentiation 8 (CD8) T cells. LpIMB19 administration led to an expansion of tumor-infiltrating CD8 T cells and improved the efficacy of anti-PD-L1 therapy. Rhamnose-rich heteropolysaccharide, a strain-specific cell wall component, was identified as the primary effector molecule of LplMB19. Toll-like receptor 2 signaling and the ability of macrophages to sequester iron were both critical for rhamnose-rich heteropolysaccharide-mediated macrophage activation upstream of the CD8 T-cell effector response and contributed to tumor cell apoptosis through iron deprivation. These findings reveal a well-defined mechanism connecting diet and health outcomes, suggesting that diet-derived commensals may warrant further investigation. Additionally, this work emphasizes the importance of strain-specific differences in studying microbiome-cancer interactions and the concept of \"nutritional immunity\" to enhance microbe-triggered antitumor immunity.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141236943","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}

引用次数: 0

HTS384 NCI60: The Next Phase of the NCI60 Screen. HTS384 NCI60：NCI60 筛选的下一阶段。

IF 12.5 1区医学

Cancer research Pub Date : 2024-08-01 DOI: 10.1158/0008-5472.CAN-23-3031

Mark W Kunkel, Nathan P Coussens, Joel Morris, Ronald C Taylor, Thomas S Dexheimer, Eric M Jones, James H Doroshow, Beverly A Teicher

{"title":"HTS384 NCI60: The Next Phase of the NCI60 Screen.","authors":"Mark W Kunkel, Nathan P Coussens, Joel Morris, Ronald C Taylor, Thomas S Dexheimer, Eric M Jones, James H Doroshow, Beverly A Teicher","doi":"10.1158/0008-5472.CAN-23-3031","DOIUrl":"10.1158/0008-5472.CAN-23-3031","url":null,"abstract":"The NCI60 human tumor cell line screen has been in operation as a service to the cancer research community for more than 30 years. The screen operated with 96-well plates, a 2-day exposure period to test agents, and following cell fixation, a visible absorbance endpoint by the protein-staining dye sulforhodamine B. In this study, we describe the next phase of this important cancer research tool, the HTS384 NCI60 screen. Although the cell lines remain the same, the updated screen is performed with 384-well plates, a 3-day exposure period to test agents, and a luminescent endpoint to measure cell viability based upon cellular ATP content. In this study, a library of 1,003 FDA-approved and investigational small-molecule anticancer agents was screened by the two NCI60 assays. The datasets were compared with a focus on targeted agents with at least six representatives in the library. For many agents, including inhibitors of EGFR, BRAF, MEK, ERK, and PI3K, the patterns of GI50 values were very similar between the screens with strong correlations between those patterns within the dataset from each screen. However, for some groups of targeted agents, including mTOR, BET bromodomain, and NAMPRTase inhibitors, there were limited or no correlations between the two datasets, although the patterns of GI50 values and correlations between those patterns within each dataset were apparent. Beginning in January 2024, the HTS384 NCI60 screen became the free screening service of the NCI to facilitate drug discovery by the cancer research community. Significance: The new NCI60 cell line screen HTS384 shows robust patterns of response to oncology agents and substantial overlap with the classic screen, providing an updated tool for studying therapeutic agents. See related commentary by Colombo and Corsello, p. 2397.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11292194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Chromosome 7 gain compensates for chromosome 10 loss in glioma. 在胶质瘤中，7 号染色体的增益可补偿 10 号染色体的缺失。

IF 12.5 1区医学

Cancer research Pub Date : 2024-07-30 DOI: 10.1158/0008-5472.CAN-24-1366

Nishanth Ulhas Nair, Alejandro A Schaffer, E Michael Gertz, Kuoyuan Cheng, Johanna Zerbib, Avinash Das Sahu, Gil Leor, Eldad D Shulman, Kenneth D Aldape, Uri Ben-David, Eytan Ruppin

{"title":"Chromosome 7 gain compensates for chromosome 10 loss in glioma.","authors":"Nishanth Ulhas Nair, Alejandro A Schaffer, E Michael Gertz, Kuoyuan Cheng, Johanna Zerbib, Avinash Das Sahu, Gil Leor, Eldad D Shulman, Kenneth D Aldape, Uri Ben-David, Eytan Ruppin","doi":"10.1158/0008-5472.CAN-24-1366","DOIUrl":"https://doi.org/10.1158/0008-5472.CAN-24-1366","url":null,"abstract":"The co-occurrence of chromosome 10 loss and chromosome 7 gain in gliomas is the most frequent loss-gain co-aneuploidy pair in human cancers. This phenomenon has been investigated since the late 1980s without resolution. Expanding beyond previous gene-centric studies, we investigated the co-occurrence in a genome-wide manner taking an evolutionary perspective. Mining of large-scale tumor aneuploidy data confirmed the previous finding of a small-scale longitudinal study that the most likely order is chromosome 10 loss followed by chromosome 7 gain. Extensive analysis of genomic and transcriptomic data from both patients and cell lines revealed that this co-occurrence can be explained by functional rescue interactions that are highly enriched on chromosome 7, which could potentially compensate for any detrimental consequences arising from the loss of chromosome 10. Transcriptomic data from various normal, non-cancerous human brain tissues were analyzed to assess which tissues may be most predisposed to tolerate compensation of chromosome 10 loss by chromosome 7 gain. The analysis indicated that the pre-existing transcriptomic states in the cortex and frontal cortex, where gliomas arise, are more favorable than other brain regions for compensation by rescuer genes that are active on chromosome 7. Collectively, these findings suggest that the phenomenon of chromosome 10 loss and chromosome 7 gain in gliomas is orchestrated by a complex interaction of many genes residing within these two chromosomes and provide a plausible reason why this co-occurrence happens preferentially in cancers originating in certain regions of the brain.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792018","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}

引用次数: 0

Multi-Dimensional Fragmentomics Enables Early and Accurate Detection of Colorectal Cancer. 多维片段组学可实现结直肠癌的早期准确检测

IF 12.5 1区医学

Cancer research Pub Date : 2024-07-29 DOI: 10.1158/0008-5472.CAN-23-3486

Yuepeng Cao, Nannan Wang, Xuxiaochen Wu, Wanxiangfu Tang, Hua Bao, Chengshuai Si, Peng Shao, Dongzheng Li, Xin Zhou, Dongqin Zhu, Shanshan Yang, Fufeng Wang, Guoqing Su, Ke Wang, Qifan Wang, Yao Zhang, Qiangcheng Wang, Dongsheng Yu, Qian Jiang, Jun Bao, Liu Yang

{"title":"Multi-Dimensional Fragmentomics Enables Early and Accurate Detection of Colorectal Cancer.","authors":"Yuepeng Cao, Nannan Wang, Xuxiaochen Wu, Wanxiangfu Tang, Hua Bao, Chengshuai Si, Peng Shao, Dongzheng Li, Xin Zhou, Dongqin Zhu, Shanshan Yang, Fufeng Wang, Guoqing Su, Ke Wang, Qifan Wang, Yao Zhang, Qiangcheng Wang, Dongsheng Yu, Qian Jiang, Jun Bao, Liu Yang","doi":"10.1158/0008-5472.CAN-23-3486","DOIUrl":"https://doi.org/10.1158/0008-5472.CAN-23-3486","url":null,"abstract":"Colorectal cancer (CRC) is frequently diagnosed in advanced stages, highlighting the need for developing approaches for early detection. Liquid biopsy using cell-free DNA (cfDNA) fragmentomics is a promising approach, but the clinical application is hindered by complexity and cost. This study aimed to develop an integrated model using cfDNA fragmentomics for accurate, cost-effective early-stage CRC detection. Plasma cfDNA was extracted and sequenced from a training cohort of 360 participants, including 176 CRC patients and 184 healthy controls. An ensemble stacked model comprising five machine learning models was employed to distinguish CRC patients from healthy controls using five cfDNA fragmentomic features. The model was validated in an independent cohort of 236 participants (117 CRC patients and 119 controls) and a prospective cohort of 242 participants (129 CRC patients and 113 controls). The ensemble stacked model showed remarkable discriminatory power between CRC patients and controls, outperforming all base models and achieving a high area under the ROC curve (AUC) of 0.986 in the validation cohort. It reached 94.88% sensitivity and 98% specificity for detecting CRC in the validation cohort, with sensitivity increasing as cancer progressed. The model also demonstrated consistently high accuracy in within-run and between-run tests and across various conditions in healthy individuals. In the prospective cohort, it achieved 91.47% sensitivity and 95.58% specificity. This integrated model capitalizes on the multiplex nature of cfDNA fragmentomics to achieve high sensitivity and robustness, offering significant promise for early CRC detection and broad patient benefit.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787264","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}

引用次数: 0

NQO1 Triggers Neutrophil Recruitment and NET formation to Drive Lung Metastasis of Invasive Breast Cancer. NQO1 触发中性粒细胞募集和 NET 形成，推动浸润性乳腺癌的肺转移

IF 12.5 1区医学

Cancer research Pub Date : 2024-07-29 DOI: 10.1158/0008-5472.CAN-24-0291

Xinzhi Wang, Yi Qu, Qianqian Xu, Zeyu Jiang, Hang Wang, Binyan Lin, Zehong Cao, Yuqi Pan, Sheng Li, Yili Hu, Hui Yang, Li He, Hang Chang, Bo Hang, Hongmei Wen, Hao Wu, Jian-Hua Mao

{"title":"NQO1 Triggers Neutrophil Recruitment and NET formation to Drive Lung Metastasis of Invasive Breast Cancer.","authors":"Xinzhi Wang, Yi Qu, Qianqian Xu, Zeyu Jiang, Hang Wang, Binyan Lin, Zehong Cao, Yuqi Pan, Sheng Li, Yili Hu, Hui Yang, Li He, Hang Chang, Bo Hang, Hongmei Wen, Hao Wu, Jian-Hua Mao","doi":"10.1158/0008-5472.CAN-24-0291","DOIUrl":"https://doi.org/10.1158/0008-5472.CAN-24-0291","url":null,"abstract":"Metastasis to the lungs is a leading cause of death for breast cancer patients. Therefore, effective therapies are urgently needed to prevent and treat breast cancer lung metastasis In this study, we uncovered a mechanism by which NAD(P)H:quinone oxidoreductase 1 (NQO1) orchestrates lung metastasis. NQO1 stabilized and upregulated peptidyl-prolyl cis-trans isomerase A (PPIA), a chaperone that regulates protein conformation and activity, by preventing its oxidation at a critical cysteine residue C161. PPIA subsequently activated CD147, a membrane protein that facilitates cell invasion. Moreover, NQO1-induced secretion of PPIA modulated the immune landscape of both primary and lung metastatic sites. Secreted PPIA engaged CD147 on neutrophils and triggered the release of neutrophil extracellular traps (NET) and neutrophil elastase, which enhanced tumor progression, invasiveness and lung colonization. Pharmacological targeting of PPIA effectively inhibited NQO1-mediated breast cancer lung metastasis. These findings reveal a previously unrecognized NQO1-PPIA-CD147-NET axis that drives breast cancer lung metastasis. Inhibiting this axis is a potential therapeutic strategy to limit lung metastasis in breast cancer patients.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787265","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}

引用次数: 0

Hyperactive DCs redirect aged anti-tumor immunity. 亢进的 DC 重定向老化的抗肿瘤免疫。

IF 12.5 1区医学

Cancer research Pub Date : 2024-07-29 DOI: 10.1158/0008-5472.CAN-24-2650

Alex C Y Chen, Debattama R Sen

{"title":"Hyperactive DCs redirect aged anti-tumor immunity.","authors":"Alex C Y Chen, Debattama R Sen","doi":"10.1158/0008-5472.CAN-24-2650","DOIUrl":"https://doi.org/10.1158/0008-5472.CAN-24-2650","url":null,"abstract":"Aging is one of the biggest risk factors for cancer development. Over 85% of all cancers occur in individuals aged over 55 years, often accompanied by age-associated immune defects. Previous studies on the tumor microenvironment (TME) during aging have identified several factors, such as the roles of fibroblasts, immunosuppression, and metastasis. However, the aging-associated defects in anti-tumor immunity, particularly regarding T cells, remain underexplored. Recent findings by Zhivaki and colleagues suggest that age-related immune defects affecting anti-tumor responses involve reduced levels of CD8+ T cells and compromised dendritic cell (DC) functions such as antigen presentation and migration. Their study demonstrates that a hyperactive DC vaccine can restore DC functions in older mice. Furthermore, these hyperactive DCs, characterized by increased IL-1β production and better migratory capability to the lymph node, promote the development of cytolytic CD4+ T cells exhibiting Th1-like phenotypes. This research reveals mechanisms underlying the response to hyperactive DC vaccines in older mice and highlights the critical role of cytolytic CD4+ T cells as substitutes for CD8+ T cells in driving anti-tumor immunity and achieving long-term tumor control in older mice.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792019","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}

引用次数: 0

Targeting YAP Activity and Glutamine Metabolism Cooperatively Suppresses Tumor Progression by Preventing Extracellular Matrix Accumulation. 靶向 YAP 活性和谷氨酰胺代谢可通过防止细胞外基质积累而协同抑制肿瘤进展

IF 12.5 1区医学

Cancer research Pub Date : 2024-07-29 DOI: 10.1158/0008-5472.CAN-23-3933

Mihyang Park, Jonghwa Jin, Da Young An, Dong-Ho Kim, Jaebon Lee, Jae Won Yun, Ilseon Hwang, Jae Seok Park, Mi Kyung Kim, You Mie Lee, Jun-Kyu Byun, Yeon-Kyung Choi, Keun-Gyu Park

{"title":"Targeting YAP Activity and Glutamine Metabolism Cooperatively Suppresses Tumor Progression by Preventing Extracellular Matrix Accumulation.","authors":"Mihyang Park, Jonghwa Jin, Da Young An, Dong-Ho Kim, Jaebon Lee, Jae Won Yun, Ilseon Hwang, Jae Seok Park, Mi Kyung Kim, You Mie Lee, Jun-Kyu Byun, Yeon-Kyung Choi, Keun-Gyu Park","doi":"10.1158/0008-5472.CAN-23-3933","DOIUrl":"https://doi.org/10.1158/0008-5472.CAN-23-3933","url":null,"abstract":"Cancer cells use multiple mechanisms to evade the effects of glutamine metabolism inhibitors. The pathways that govern responses to alterations in glutamine availability within the tumor may represent therapeutic targets for combinatorial strategies with these inhibitors. Here, we showed that targeting glutamine utilization stimulated Yes-associated protein (YAP) signaling in cancer cells by reducing cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)-dependent phosphorylation of large tumor suppressor (LATS). Elevated YAP activation induced extracellular matrix (ECM) deposition by increasing secretion of connective tissue growth factor (CTGF) that promoted production of fibronectin and collagen by surrounding fibroblasts. Consequently, inhibiting YAP synergized with inhibition of glutamine utilization to effectively suppress tumor growth in vivo, along with a concurrent decrease in ECM deposition. Blocking ECM remodeling also augmented the tumor suppressive effects of the glutamine utilization inhibitor. Collectively, these data reveal mechanisms by which targeting glutamine utilization increases ECM accumulation and identify potential strategies to reduce ECM levels and increase the efficacy of glutamine metabolism inhibitors.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787266","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}

引用次数: 0

FOXP4 is a Direct YAP1 Target that Promotes Gastric Cancer Stemness and Drives Metastasis. FOXP4是YAP1的直接靶标，可促进胃癌干细胞生长并推动转移

IF 12.5 1区医学

Cancer research Pub Date : 2024-07-24 DOI: 10.1158/0008-5472.CAN-23-3074

Xiaoli Liu, Bonan Chen, Fuda Xie, Kit Yee Wong, Alvin Ho-Kwan Cheung, Jinglin Zhang, Qian Wu, Canbin Fang, Jintao Hu, Shouyu Wang, Dazhi Xu, Jianwu Chen, Yuzhi Wang, Chi Chun Wong, Huarong Chen, William Ka Kei Wu, Jun Yu, Michael W Y Chan, Chi Man Tsang, Kwok Wai Lo, Gary M K Tse, Ka-Fai To, Wei Kang

{"title":"FOXP4 is a Direct YAP1 Target that Promotes Gastric Cancer Stemness and Drives Metastasis.","authors":"Xiaoli Liu, Bonan Chen, Fuda Xie, Kit Yee Wong, Alvin Ho-Kwan Cheung, Jinglin Zhang, Qian Wu, Canbin Fang, Jintao Hu, Shouyu Wang, Dazhi Xu, Jianwu Chen, Yuzhi Wang, Chi Chun Wong, Huarong Chen, William Ka Kei Wu, Jun Yu, Michael W Y Chan, Chi Man Tsang, Kwok Wai Lo, Gary M K Tse, Ka-Fai To, Wei Kang","doi":"10.1158/0008-5472.CAN-23-3074","DOIUrl":"https://doi.org/10.1158/0008-5472.CAN-23-3074","url":null,"abstract":"The Hippo-YAP1 pathway is an evolutionally conserved signaling cascade that controls organ size and tissue regeneration. Dysregulation of Hippo-YAP1 signaling promotes initiation and progression of several types of cancer, including gastric cancer (GC). As the Hippo-YAP1 pathway regulates expression of thousands of genes, it is important to establish which target genes contribute to the oncogenic program driven by YAP1 to identify strategies to circumvent it. Here, we identified a vital role of FOXP4 in YAP1-driven gastric carcinogenesis by maintaining stemness and promoting peritoneal metastasis. Loss of FOXP4 impaired GC spheroid formation and reduced stemness marker expression, while FOXP4 upregulation potentiated cancer cell stemness. RNA-seq analysis revealed SOX12 as downstream target of FOXP4, and functional studies established that SOX12 supports stemness in YAP1-induced carcinogenesis. A small molecule screen identified 42-(2-Tetrazolyl)rapamycin as a FOXP4 inhibitor, and targeting FOXP4 suppressed GC tumor growth and enhanced the efficacy of 5-FU chemotherapy in vivo. Collectively, these findings revealed that FOXP4 upregulation by YAP1 in GC regulates stemness and tumorigenesis by upregulating SOX12. Targeting the YAP1-FOXP4-SOX12 axis represents a potential therapeutic strategy for GC.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757222","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}

引用次数: 0

AFDN deficiency promotes liver tropism of metastatic colorectal cancer. AFDN 缺乏会促进转移性结直肠癌的肝趋向性。

IF 12.5 1区医学

Cancer research Pub Date : 2024-07-24 DOI: 10.1158/0008-5472.CAN-23-3140

Shaoxia Liao, Jingwen Deng, Mengli Deng, Chaoyi Chen, Fengyan Han, Kehong Ye, Chenxia Wu, Lvyuan Pan, Maode Lai, Zhe Tang, Honghe Zhang

{"title":"AFDN deficiency promotes liver tropism of metastatic colorectal cancer.","authors":"Shaoxia Liao, Jingwen Deng, Mengli Deng, Chaoyi Chen, Fengyan Han, Kehong Ye, Chenxia Wu, Lvyuan Pan, Maode Lai, Zhe Tang, Honghe Zhang","doi":"10.1158/0008-5472.CAN-23-3140","DOIUrl":"https://doi.org/10.1158/0008-5472.CAN-23-3140","url":null,"abstract":"Liver metastasis is a major cause of morbidity and mortality in patients with colorectal cancer. A better understanding of the biological mechanisms underlying liver tropism and metastasis in colorectal cancer could help to identify improved prevention and treatment strategies. In this study, we performed genome-side CRISPR loss-of-function screening in a mouse colorectal cancer model and identified deficiency of AFDN, a protein involved in establishing and maintaining cell-cell contacts, as a driver of liver metastasis. Elevated AFDN expression was correlated with prolonged survival in patients with colorectal cancer. AFDN-deficient colorectal cancer cells preferentially metastasized to the liver but not in the lungs. AFDN loss in colorectal cancer cells at the primary site promoted cancer cell migration and invasion by disrupting tight intercellular junctions. Additionally, CXCR4 expression was increased in AFDN-deficient colorectal cancer cells via the JAK-STAT signaling pathway, which reduced the motility of AFDN-deficient colorectal cancer cells and facilitated their colonization of the liver. Collectively, these data shed light on the mechanism by which AFDN deficiency promotes liver tropism in metastatic colorectal cancer.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757221","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}

引用次数: 0