Oncogene最新文献_第3页

Frequent copy number gain of MCL1 is a therapeutic target for osteosarcoma. 频繁的MCL1拷贝数增加是骨肉瘤的治疗靶点。

IF 6.9 1区医学

Oncogene Pub Date : 2024-12-11 DOI: 10.1038/s41388-024-03251-6

Satoshi Takagi, Mikako Nakajima, Sumie Koike, Miho Takami, Yoshiya Sugiura, Seiji Sakata, Satoko Baba, Ai Takemoto, Tianyi Huang, Yosuke Seto, Masanori Saito, Yuki Funauchi, Keisuke Ae, Kengo Takeuchi, Naoya Fujita, Ryohei Katayama

{"title":"Frequent copy number gain of MCL1 is a therapeutic target for osteosarcoma.","authors":"Satoshi Takagi, Mikako Nakajima, Sumie Koike, Miho Takami, Yoshiya Sugiura, Seiji Sakata, Satoko Baba, Ai Takemoto, Tianyi Huang, Yosuke Seto, Masanori Saito, Yuki Funauchi, Keisuke Ae, Kengo Takeuchi, Naoya Fujita, Ryohei Katayama","doi":"10.1038/s41388-024-03251-6","DOIUrl":"https://doi.org/10.1038/s41388-024-03251-6","url":null,"abstract":"Osteosarcoma (OS) is a primary malignant bone tumor primarily affecting children and adolescents. The lack of progress in drug development for OS is partly due to unidentified actionable oncogenic drivers common to OS. In this study, we demonstrate that copy number gains of MCL1 frequently occur in OS, leading to vulnerability to therapies based on Mcl-1 inhibitors. Fluorescence in situ hybridization analysis of 41 specimens revealed MCL1 amplification in 46.3% of patients with OS. Genetic inhibition of MCL1 induced significant apoptosis in MCL1-amplified OS cells, and the pharmacological efficacy of Mcl-1 inhibitors was correlated with MCL1 copy numbers. Chromosome 1q21.2-3 region, where MCL1 is located, contains multiple genes related to the IGF-1R/PI3K pathway, including PIP5K1A, TARS2, OUTD7B, and ENSA, which also showed increased copy numbers in MCL1-amplified OS cells. Furthermore, combining Mcl-1 inhibitors with IGF-1R inhibitors resulted in synergistic cell death by overcoming drug tolerance conferred by the activation of IGF signaling and suppressed tumor growth in MCL1-amplified OS xenograft models. These results suggest that genomic amplification of MCL1 in the 1q21.2-3 region, which occurred in approximately half of OS patients, may serve as a predictive biomarker for the combination therapy with an Mcl-1 inhibitor and an IGF1R inhibitor.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813816","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

Tissue factor promotes TREX1 protein stability to evade cGAS-STING innate immune response in pancreatic ductal adenocarcinoma. 组织因子促进TREX1蛋白稳定性以逃避胰腺导管腺癌的cGAS-STING先天免疫反应。

IF 6.9 1区医学

Oncogene Pub Date : 2024-12-10 DOI: 10.1038/s41388-024-03248-1

Yinyin Xue, Yue Wang, Zhiqiang Ren, Ker Yu

{"title":"Tissue factor promotes TREX1 protein stability to evade cGAS-STING innate immune response in pancreatic ductal adenocarcinoma.","authors":"Yinyin Xue, Yue Wang, Zhiqiang Ren, Ker Yu","doi":"10.1038/s41388-024-03248-1","DOIUrl":"https://doi.org/10.1038/s41388-024-03248-1","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) remains the most challenging human malignancy that urgently needs effective therapy. Tissue factor (TF) is expressed in ~80% of PDAC and represents a potential therapeutic target. While a novel TF-ADC (MRG004A) demonstrated efficacy for PDAC and TNBC in a Phase I/II trial [Ref. 18], the functional role of TF in PDAC remains incompletely understood. We investigated the relationship between TF and the innate STING pathway. We found that patients with TF-overexpression had poor survival, very low levels of P-STING/P-TBK1, reduced amounts of ISGs and chemokines as well as low numbers of cytotoxic immunocytes in their tumor. In experimental models of mouse and human PDAC, tumor cell-intrinsic TF expression played a major role in silencing the cytosolic micronuclei sensing and cGAS-STING activation. This process involved a TREX1 exonuclease-dependent clearance of micronucleus-DNA accumulated in tumor cells. Treatment of tumors with TF-KO/shRNA or anti-TF antibody HuSC1-39 (parent antibody of MRG004A) triggered a rapid and proteasome-dependent degradation of TREX1 thereby restoring the STING/TBK1 cascade phosphorylation. TF-inhibition therapy promoted a robust STING/IRF3-dependent IFN/CCL5/CXCL9-11 production, immune effector cell infiltration and antitumor efficacy. Moreover, in the PBMC and cancer cell co-culture, TF-inhibition synergized with a STING agonist compound. A covalently conjugated TF antibody-STING agonist ADC strongly increased the efficacy of tumor-targeted STING agonism on chemokine secretion and tumor inhibition in vitro and in vivo. Thus, TF-inhibition reshapes an \"immune hot\" tumor environment. TF-targeted therapy warrants clinical investigation as a single agent or in combination with immunotherapy for treating TF-positive PDAC and TNBC.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807690","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

TFF3 drives Hippo dependent EGFR-TKI resistance in lung adenocarcinoma. TFF3驱动肺腺癌中Hippo依赖性EGFR-TKI耐药。

IF 6.9 1区医学

Oncogene Pub Date : 2024-12-10 DOI: 10.1038/s41388-024-03244-5

Shuwei Zhang, Yan Qin Tan, Xi Zhang, Basappa Basappa, Tao Zhu, Vijay Pandey, Peter E Lobie

{"title":"TFF3 drives Hippo dependent EGFR-TKI resistance in lung adenocarcinoma.","authors":"Shuwei Zhang, Yan Qin Tan, Xi Zhang, Basappa Basappa, Tao Zhu, Vijay Pandey, Peter E Lobie","doi":"10.1038/s41388-024-03244-5","DOIUrl":"10.1038/s41388-024-03244-5","url":null,"abstract":"Intrinsic and acquired resistance represent major obstacles to optimize outcomes in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeted therapy in lung adenocarcinoma (LUAD). Hence, a deeper understanding of EGFR-TKI resistance mechanisms in LUAD will potentially assist in formulating strategies to delay or overcome such resistance. Herein, it was observed that trefoil factor 3 (TFF3) is a crucial mediator of the LUAD EGFR-TKI response. TFF3 conferred intrinsic resistance to EGFR inhibition in LUAD by promotion of EGFR activation. TFF3 expression was also increased in acquired EGFR-TKI resistant LUAD, accompanied by reduced EGFR activation. YAP, a key mediator of the Hippo signaling, was positively regulated by TFF3 by post-transcriptional mechanisms and was responsible for acquired EGFR-TKI resistance mediated by TFF3. Inhibition of TFF3 by a small molecule inhibitor not only enhanced EGFR-TKI sensitivity in LUAD cells but also restored the sensitivity of acquired EGFR-TKI resistant LUAD cells to EGFR-TKIs in vitro and in vivo. These findings demonstrate a pivotal function of TFF3 in mediating both intrinsic and acquired EGFR-TKI resistance in LUAD and may offer a potential therapeutic mechanism for delaying or overcoming resistance to EGFR-TKIs.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807687","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

Pseudokinase TRIB3 stabilizes SSRP1 via USP10-mediated deubiquitination to promote multiple myeloma progression. 假激酶TRIB3通过usp10介导的去泛素化来稳定SSRP1，促进多发性骨髓瘤的进展。

IF 6.9 1区医学

Oncogene Pub Date : 2024-12-09 DOI: 10.1038/s41388-024-03245-4

Haiqin Wang, Long Liang, Yifang Xie, Han Gong, Feifan Fan, Chengcai Wen, Yu Jiang, Shiying Lei, Xili Qiu, Hongling Peng, Mao Ye, Xiaojuan Xiao, Jing Liu

{"title":"Pseudokinase TRIB3 stabilizes SSRP1 via USP10-mediated deubiquitination to promote multiple myeloma progression.","authors":"Haiqin Wang, Long Liang, Yifang Xie, Han Gong, Feifan Fan, Chengcai Wen, Yu Jiang, Shiying Lei, Xili Qiu, Hongling Peng, Mao Ye, Xiaojuan Xiao, Jing Liu","doi":"10.1038/s41388-024-03245-4","DOIUrl":"https://doi.org/10.1038/s41388-024-03245-4","url":null,"abstract":"Multiple myeloma (MM), the world's second most common hematologic malignancy, poses considerable clinical challenges due to its aggressive progression and resistance to therapy. Addressing these challenges requires a detailed understanding of the mechanisms driving MM initiation, progression, and therapeutic resistance. This study identifies the pseudokinase tribble homolog 3 (TRIB3) as a high-risk factor that promotes MM malignancy in vitro and in vivo. Mechanistically, TRIB3 directly interacts with structure-specific recognition protein 1 (SSRP1) and ubiquitin-specific peptidase 10 (USP10), facilitating the formation of a TRIB3/USP10/SSRP1 ternary complex. This complex stabilizes SSRP1 via USP10-mediated deubiquitination, thereby driving MM cell proliferation. Furthermore, a stapled peptide, SP-A, was developed, which effectively disrupts the TRIB3/USP10/SSRP1 complex, leading to a decrease in SSRP1 levels by inhibiting its stabilization through USP10. Notably, SP-A exhibits strong synergistic effects when combined with the proteasome inhibitor bortezomib. Given the critical role of the TRIB3/USP10/SSRP1 complex in MM pathophysiology, it represents a promising therapeutic target for MM treatment. In MM cells, TRIB3, USP10 and SSRP1 form a ternary complex and TRIB3 enhances the deubiquitinating effect of USP10 on SSRP1, leading to malignant progression of MM. In the case of drug intervention, SP-A attenuates the binding of SSRP1 and USP10 by inhibiting protein interactions between TRIB3 and SSRP1 and promoted SSRP1 protein degradation, leading to significant inhibition of MM development. Visual abstract created with Biorender.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801406","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

SPTLC2 drives an EGFR-FAK-HBEGF signaling axis to promote ovarian cancer progression. SPTLC2驱动EGFR-FAK-HBEGF信号轴促进卵巢癌进展。

IF 6.9 1区医学

Oncogene Pub Date : 2024-12-07 DOI: 10.1038/s41388-024-03249-0

Xingyue Zhai, Ning Shen, Tao Guo, Jianxin Wang, Chunrui Xie, Yukai Cao, Ling Liu, Yumei Yan, Songshu Meng, Sha Du

{"title":"SPTLC2 drives an EGFR-FAK-HBEGF signaling axis to promote ovarian cancer progression.","authors":"Xingyue Zhai, Ning Shen, Tao Guo, Jianxin Wang, Chunrui Xie, Yukai Cao, Ling Liu, Yumei Yan, Songshu Meng, Sha Du","doi":"10.1038/s41388-024-03249-0","DOIUrl":"https://doi.org/10.1038/s41388-024-03249-0","url":null,"abstract":"The epidermal growth factor receptor (EGFR) signaling pathway is frequently associated with ovarian cancer (OC) progression. However, inhibition of EGFR signaling in OC patients achieved limited therapeutic effects, highlighting the need to define the mechanism of EGFR deregulation in OC development. Herein we showed that serine palmitoyltransferase long chain base subunit 2 (SPTLC2) acts as a positive regulator in the EGFR signaling pathway in OC. Phenotypically, depletion of SPTLC2 suppressed clonogenic growth and migration of OC cells in vitro and in ovo, as well as metastasis in OC xenograft models, whereas overexpression of SPTLC2 yielded opposite effects. Mechanistically, SPTLC2 drives an EGFR-FAK-HBEGF signaling axis via binding with EGFR. Notably, the serine palmitoyltransferase activity of SPTLC2 is critical for regulation of the EGFR-FAK-HBEGF signaling axis and activity in OC progression. Clinically, high SPTLC2 expression is associated with high-grade serous ovarian cancer and metastasis. Collectively, our findings establish an oncogenic role of SPTLC2 in OC growth and progression though upregulation of EGFR signaling and suggest that SPTLC2 represents a potential therapeutic target in EGFR-driven ovarian cancer patients.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792163","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

Metabolic imaging distinguishes ovarian cancer subtypes and detects their early and variable responses to treatment. 代谢成像区分卵巢癌亚型，并检测其早期和可变的治疗反应。

IF 6.9 1区医学

Oncogene Pub Date : 2024-12-06 DOI: 10.1038/s41388-024-03231-w

Ming Li Chia, Flaviu Bulat, Adam Gaunt, Susana Ros, Alan J Wright, Ashley Sawle, Luca Porcu, Maria Vias, James D Brenton, Kevin M Brindle

{"title":"Metabolic imaging distinguishes ovarian cancer subtypes and detects their early and variable responses to treatment.","authors":"Ming Li Chia, Flaviu Bulat, Adam Gaunt, Susana Ros, Alan J Wright, Ashley Sawle, Luca Porcu, Maria Vias, James D Brenton, Kevin M Brindle","doi":"10.1038/s41388-024-03231-w","DOIUrl":"https://doi.org/10.1038/s41388-024-03231-w","url":null,"abstract":"High grade serous ovarian cancer displays two metabolic subtypes; a high OXPHOS subtype that shows increased expression of genes encoding electron transport chain components, increased oxygen consumption, and increased chemosensitivity, and a low OXPHOS subtype that exhibits glycolytic metabolism and is more drug resistant. We show here in patient-derived organoids and in the xenografts obtained by their subcutaneous implantation that the low OXPHOS subtype shows higher lactate dehydrogenase activity and monocarboxylate transporter 4 expression than the high OXPHOS subtype and increased lactate labeling in 13C magnetic resonance spectroscopy (MRS) measurements of hyperpolarized [1-13C]pyruvate metabolism. There was no difference between the subtypes in PET measurements of 2-deoxy-2-[fluorine-18]fluoro-D-glucose ([18F]FDG) uptake. Both metabolic imaging techniques could detect the early response to Carboplatin treatment in drug-sensitive high OXPHOS xenografts and no response in drug-resistant in low OXPHOS xenografts. 13C magnetic resonance spectroscopic imaging of hyperpolarized [1-13C]pyruvate metabolism has the potential to be used clinically to distinguish low OXPHOS and high OXPHOS tumor deposits in HGSOC patients and to detect their differential responses to treatment.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786152","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

LGALS9B stabilizes EEF1D protein and activates the PI3K/AKT signaling pathway to promote gastric cancer occurrence and metastasis. LGALS9B稳定EEF1D蛋白，激活PI3K/AKT信号通路，促进胃癌发生转移。

IF 6.9 1区医学

Oncogene Pub Date : 2024-12-05 DOI: 10.1038/s41388-024-03247-2

Huolun Feng, Wei Yao, Yucheng Zhang, Yongfeng Liu, Bin Liu, Ji Zhou, Jiehui Li, Zhuosheng Jiang, Fa Ling, Jianlong Zhou, Deqing Wu, Yong Li, Juan Yang, Jiabin Zheng

{"title":"LGALS9B stabilizes EEF1D protein and activates the PI3K/AKT signaling pathway to promote gastric cancer occurrence and metastasis.","authors":"Huolun Feng, Wei Yao, Yucheng Zhang, Yongfeng Liu, Bin Liu, Ji Zhou, Jiehui Li, Zhuosheng Jiang, Fa Ling, Jianlong Zhou, Deqing Wu, Yong Li, Juan Yang, Jiabin Zheng","doi":"10.1038/s41388-024-03247-2","DOIUrl":"https://doi.org/10.1038/s41388-024-03247-2","url":null,"abstract":"Gastric cancer ranks among the most prevalent malignancies globally, characterized by limited treatment efficacy and high recurrence rates. Effective management of this disease requires a comprehensive understanding of its underlying pathogenic mechanisms. Galectins have emerged as promising targets in gastric cancer therapy, with Galectin-9 (LGALS9) receiving considerable attention in recent years. However, Galectin-9B (LGALS9B) remains relatively under-explored in gastric cancer research. Our study investigates the role of LGALS9B in gastric cancer progression, demonstrating that its over-expression enhances cellular proliferation, migration, and invasion, while its knockdown inhibits these processes both in vitro and in vivo. We further elucidate that LGALS9B competes with the E3 ligase HERC5 for binding to eukaryotic translation elongation factor 1 delta (EEF1D), thereby preventing its protein degradation. This interaction results in the enrichment of EEF1D, which activates the PI3K/AKT signaling pathway and ultimately promotes gastric cancer progression. These findings highlight the regulatory role of LGALS9B in the pathogenesis of gastric cancer, offering valuable insights into potential novel therapeutic strategies for managing this challenging disease.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786098","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

BEX4 inhibits the progression of clear cell renal cell carcinoma by stabilizing SH2D4A, which is achieved by blocking SIRT2 activity. BEX4通过稳定SH2D4A抑制透明细胞肾细胞癌的进展，这是通过阻断SIRT2活性实现的。

IF 6.9 1区医学

Oncogene Pub Date : 2024-12-05 DOI: 10.1038/s41388-024-03235-6

Ziyao Li, Shiyong Xin, Liqun Huang, Ye Tian, Weihua Chen, Xiang Liu, Bowen Ye, Rong Bai, Guosheng Yang, Wenwen Wang, Lin Ye

{"title":"BEX4 inhibits the progression of clear cell renal cell carcinoma by stabilizing SH2D4A, which is achieved by blocking SIRT2 activity.","authors":"Ziyao Li, Shiyong Xin, Liqun Huang, Ye Tian, Weihua Chen, Xiang Liu, Bowen Ye, Rong Bai, Guosheng Yang, Wenwen Wang, Lin Ye","doi":"10.1038/s41388-024-03235-6","DOIUrl":"10.1038/s41388-024-03235-6","url":null,"abstract":"Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies. Recently, the role of brain-expressed X-linked 4 (BEX4) in cancer progression has received increasing attention. This study aimed to investigate the function of BEX4 in ccRCC and to reveal the underlying mechanisms. We first confirmed that BEX4 was significantly downregulated in ccRCC by bioinformatics analysis and that patients with low BEX4 expression tended to have prolonged overall survival time. Subsequently, we confirmed that BEX4 inhibited ccRCC cell proliferation in vitro and tumorigenesis in vivo through a series of cell function assays and the establishment of a nude mouse xenograft model, respectively. Mechanistically, we found that BEX4 positively regulates the expression of Src homology 2 domain-containing 4A (SH2D4A), an inhibitor of the NOTCH pathway, which further promoted the tumor-suppressive effects of BEX4. In addition, our study confirmed that the promoting effect of BEX4 on SH2D4A was achieved by inhibiting the deacetylase sirtuin 2 (SIRT2) activity. On this basis, we found that there was a competition between acetylation and ubiquitination modifications at the K69 site of SH2DA4 and that BEX4-induced upregulation of acetylation at the k69 site stabilizes SH2D4A protein expression by inhibiting ubiquitination at the same site. In addition, dual-luciferase assays showed that the transcriptional activity of BEX4 was positively regulated by activation transcription factor 3 (ATF3). Our study suggests that BEX4 plays a role in inhibiting tumor progression in ccRCC and maybe a new diagnostic and therapeutic target for ccRCC patients.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785808","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

JAK2/ULK1 axis promotes cervical cancer progression by autophagy induction and SRPK1 phosphorylation. JAK2/ULK1轴通过自噬诱导和SRPK1磷酸化促进宫颈癌进展。

IF 6.9 1区医学

Oncogene Pub Date : 2024-12-04 DOI: 10.1038/s41388-024-03246-3

Qiuhong Duan, Wei Wang, Hua Xiong, Juanjuan Xiao, Han Xiao, Feng Zhu, Hui Lu

引用次数: 0

Breast cancer stem cell-derived exosomal lnc-PDGFD induces fibroblast-niche formation and promotes lung metastasis. 乳腺癌干细胞来源外泌体lnc-PDGFD诱导成纤维细胞生态位形成并促进肺转移。

IF 6.9 1区医学

Oncogene Pub Date : 2024-12-04 DOI: 10.1038/s41388-024-03237-4

Tingting Tang, Tao Yang, Huijie Xue, Xiao Liu, Jie Yu, Chen Liang, Dameng Li, Chenxi Xiang, Junnian Zheng, Liang Wei, Bo Ma

{"title":"Breast cancer stem cell-derived exosomal lnc-PDGFD induces fibroblast-niche formation and promotes lung metastasis.","authors":"Tingting Tang, Tao Yang, Huijie Xue, Xiao Liu, Jie Yu, Chen Liang, Dameng Li, Chenxi Xiang, Junnian Zheng, Liang Wei, Bo Ma","doi":"10.1038/s41388-024-03237-4","DOIUrl":"https://doi.org/10.1038/s41388-024-03237-4","url":null,"abstract":"Triple-negative breast cancer (TNBC) is the most aggressive subtype with high metastatic potential and lack of therapeutic targets. Breast cancer stem cells (BCSCs) are enriched in TNBC and contribute to its metastatic propensity. Accumulating evidence suggests that cancer-derived exosomes are key drivers of premetastatic niche formation in distal organs. However, the function and underlying mechanism of BCSC-derived exosomes in TNBC metastasis remain elusive. Here, we demonstrated that BCSC-derived exosomes exhibit a greater capacity to activate fibroblasts and promote TNBC cell metastasis to the lung than non-BCSC-derived exosomes. Additionally, we found that upregulation of exosomal long non-coding RNA platelet derived growth factor D (lnc-PDGFD) expression in BCSCs is responsible for fibroblast activation through YBX1/NF-kB signaling in the lung. Activated fibroblasts further promote tumor progression by secreting IL-11. Taken together, BCSC-derived exosomes enriched with lnc-PDGFD could activate fibroblasts, thereby facilitating lung metastasis in TNBC patients. These results provide new insights into the mechanism of TNBC metastasis to the lung.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780779","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