Cancer Science最新文献_第2页

Highly hypofractionated biaxially rotational dynamic radiation therapy (BROAD-RT) for high-risk prostate cancer. 高度低分割双轴旋转动态放疗（BROAD-RT）治疗高危前列腺癌。

IF 5.7 2区医学

Cancer Science Pub Date : 2025-01-20 DOI: 10.1111/cas.16429

Rihito Aizawa, Takashi Ogata, Takayuki Goto, Kiyonao Nakamura, Kenji Takayama, Ryo Ashida, Yuki Kita, Takayuki Sumiyoshi, Kaoru Murakami, Kei Mizuno, Takashi Kobayashi, Takashi Mizowaki

{"title":"Highly hypofractionated biaxially rotational dynamic radiation therapy (BROAD-RT) for high-risk prostate cancer.","authors":"Rihito Aizawa, Takashi Ogata, Takayuki Goto, Kiyonao Nakamura, Kenji Takayama, Ryo Ashida, Yuki Kita, Takayuki Sumiyoshi, Kaoru Murakami, Kei Mizuno, Takashi Kobayashi, Takashi Mizowaki","doi":"10.1111/cas.16429","DOIUrl":"https://doi.org/10.1111/cas.16429","url":null,"abstract":"To report clinical outcomes following highly hypofractionated biaxially rotational dynamic radiation therapy (BROAD-RT), a unique radiation therapy method that facilitates non-coplanar volumetric-modulated arc therapy (VMAT) without the need to rotate the couch or reposition the patient, for high-risk prostate cancer (PCa) with simultaneous integrated boost (SIB) for intra-prostatic dominant lesions (IPDLs), we performed a single-center prospective pilot study. In this study, patients with high-risk PCa according to the D'Amico classification or those with cT3aN0M0 PCa were eligible. VMAT was performed using BROAD-RT, and a dose of 54 Gy in 15 fractions was prescribed for the prostate in combination with SIB for IPDLs at a dose of 57 Gy in 15 fractions. Short-term neoadjuvant androgen-deprivation therapy (median: 6.9 months) was conducted. Neither adjuvant androgen-deprivation therapy nor fiducial marker implantation to the prostate was applied for any patient. In total, 26 patients were registered in this study between August 2018 and November 2020. Their median age was 73 years at the initiation of RT. The median follow-up period was 49.7 months. The 4-year cumulative incidence rates of grade 2 late GU and GI toxicities were 15.4 and 3.8%, respectively. No grade 3 or higher acute or late toxicities were observed. The 4-year biochemical failure-free survival rates were 87.7%. In conclusion, highly hypofractionated RT using BROAD-RT for high-risk PCa with SIB for IPDLs was feasible and facilitated favorable oncological outcomes. Therefore, this approach is considered a promising method to achieve safe dose escalation and shorten the treatment duration.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Multiple Kinase Small Molecule Inhibitor Tinengotinib (TT-00420) Alone or With Chemotherapy Inhibit the Growth of SCLC. 多激酶小分子抑制剂Tinengotinib （TT-00420）单独或联合化疗抑制SCLC的生长。

IF 5.7 2区医学

Cancer Science Pub Date : 2025-01-16 DOI: 10.1111/cas.16450

Hui Li, Chenchen Tang, Peiyan Zhao, Rui Zhong, Yuanhua Lu, Yan Liu, Rixin Li, Shaowei Lan, Chunjiao Wu, Xiaoyan Qiang, Peng Peng, Frank Wu, Ying Cheng, Ying Liu

{"title":"Multiple Kinase Small Molecule Inhibitor Tinengotinib (TT-00420) Alone or With Chemotherapy Inhibit the Growth of SCLC.","authors":"Hui Li, Chenchen Tang, Peiyan Zhao, Rui Zhong, Yuanhua Lu, Yan Liu, Rixin Li, Shaowei Lan, Chunjiao Wu, Xiaoyan Qiang, Peng Peng, Frank Wu, Ying Cheng, Ying Liu","doi":"10.1111/cas.16450","DOIUrl":"https://doi.org/10.1111/cas.16450","url":null,"abstract":"There is an urgent need to develop new targeted treatment agents for small cell lung cancer (SCLC). Tinengotinib (TT-00420) is a novel, multi-targeted, and spectrally selective small-molecule kinase inhibitor that has shown significant inhibitory effects on certain solid tumors in preclinical studies. However, its role and mechanism of action in SCLC remain unclear. In this study, we demonstrated that tinengotinib effectively inhibited SCLC cell proliferation, especially highly expressing NeuroD1 (SCLC-N), in the SCLC cell line-derived xenograft (CDX) model and the malignant pleural effusion cell model of patients with SCLC. When combined with etoposide/cisplatin, it synergistically inhibited SCLC growth. Tinengotinib regulates proliferation, apoptosis, migration, cell cycle and angiogenesis in SCLC cells. Mechanistic studies revealed that c-Myc expression may be a key factor influencing the effect of tinengotinib in SCLC-N. This study provides reliable preclinical data and a new direction for tinengotinib as a promising therapy for SCLC, either alone or in combination with chemotherapy.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Mutation Analysis of TMB-High Colorectal Cancer: Insights Into Molecular Pathways and Clinical Implications. tmb -高结直肠癌的突变分析：分子途径和临床意义。

IF 5.7 2区医学

Cancer Science Pub Date : 2025-01-16 DOI: 10.1111/cas.16455

Yuko Chikaishi, Hiroshi Matsuoka, Eiji Sugihara, Mayu Takeda, Makoto Sumitomo, Seiji Yamada, Gaku Inaguma, Yusuke Omura, Yeongcheol Cheong, Yosuke Kobayashi, Masaya Nakauchi, Junichiro Hiro, Koji Masumori, Koki Otsuka, Hiroshi Nishihara, Koichi Suda, Hideyuki Saya, Tetsuya Takimoto

{"title":"Mutation Analysis of TMB-High Colorectal Cancer: Insights Into Molecular Pathways and Clinical Implications.","authors":"Yuko Chikaishi, Hiroshi Matsuoka, Eiji Sugihara, Mayu Takeda, Makoto Sumitomo, Seiji Yamada, Gaku Inaguma, Yusuke Omura, Yeongcheol Cheong, Yosuke Kobayashi, Masaya Nakauchi, Junichiro Hiro, Koji Masumori, Koki Otsuka, Hiroshi Nishihara, Koichi Suda, Hideyuki Saya, Tetsuya Takimoto","doi":"10.1111/cas.16455","DOIUrl":"https://doi.org/10.1111/cas.16455","url":null,"abstract":"Colorectal cancer (CRC) is well characterized in terms of genetic mutations and the mechanisms by which they contribute to carcinogenesis. Mutations in APC, TP53, and KRAS are common in CRC, indicating key roles for these genes in tumor development and progression. However, for certain tumors with low frequencies of these mutations that are defined by tumor location and molecular phenotypes, a carcinogenic mechanism dependent on BRAF mutations has been proposed. We here analyzed targeted sequence data linked to clinical information for CRC, focusing on tumors with a high tumor mutation burden (TMB) in order to identify the characteristics of associated mutations, their relations to clinical features, and the mechanisms of carcinogenesis in tumors lacking the major driver oncogenes. Analysis of overall mutation frequencies confirmed that APC, TP53, and KRAS mutations were the most prevalent in our cohort. Compared with other tumors, TMB-high tumors were more frequent on the right side of the colon, had lower KRAS and higher BRAF mutation frequencies as well as a higher microsatellite instability (MSI) score, and showed a greater contribution of a mutational signature associated with MSI. Ranking of variant allele frequencies to identify genes that play a role early in carcinogenesis suggested that mutations in genes related to the DNA damage response (such as ATM and POLE) and to MSI (such as MSH2 and MSH6) may precede BRAF mutations associated with activation of the serrated pathway in TMB-high tumors. Our results thus indicate that TMB-high tumors suggest that mutations of genes related to mismatch repair and the DNA damage response may contribute to activation of the serrated pathway in CRC.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

A 37-Year Retrospective Analysis Reveals a High Rate of Cutaneous Angiosarcoma of the Scalp in Okinawa, Japan. 一项37年的回顾性分析显示，日本冲绳地区头皮皮肤血管肉瘤的发病率很高。

IF 5.7 2区医学

Cancer Science Pub Date : 2025-01-16 DOI: 10.1111/cas.16453

Aoi Ohira, Daisuke Utsumi, Ryoko Awazawa, Nobutake Yagi, Tsuyoshi Awazawa, Sayaka Yamaguchi, Teruki Yanagi, Kenzo Takahashi

{"title":"A 37-Year Retrospective Analysis Reveals a High Rate of Cutaneous Angiosarcoma of the Scalp in Okinawa, Japan.","authors":"Aoi Ohira, Daisuke Utsumi, Ryoko Awazawa, Nobutake Yagi, Tsuyoshi Awazawa, Sayaka Yamaguchi, Teruki Yanagi, Kenzo Takahashi","doi":"10.1111/cas.16453","DOIUrl":"https://doi.org/10.1111/cas.16453","url":null,"abstract":"Angiosarcoma (AS) is a rare, aggressive malignancy originating from vascular or lymphatic endothelial cells. Despite its severity, little is known about its epidemiology, and no geographical regions have previously been identified as having an exceptionally high incidence. We retrospectively analyzed medical records spanning 37 years (1987-2023) in Okinawa, Japan, identifying 135 cases of AS that were used to calculate its incidence. This incidence was compared to global data to highlight significant regional differences. Factors related to patients' survival were also assessed. The age-adjusted incidence of AS of the scalp in Okinawa was 4.1 per million per year (mpy; 2015 Japanese model population) or 2.0 per mpy (2000 US standard population), significantly higher than the global data, including in the United States (about eightfold higher) and mainland Japan (about fourfold higher). The estimated five-year survival for patients with AS of the scalp in Okinawa was 9.2%. Multivariate analysis identified surgery, chemotherapy, and radiotherapy as significant factors associated with patient survival. This study provides the first evidence of a significantly higher incidence rate of AS of the scalp in Okinawa. Given its rarity, further research is crucial to uncover the epidemiological, genetic, and environmental factors driving this cancer.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

IGF2BP3 Triggers STAT3 Pathway by Stabilizing SRC RNA in an m6A-Dependent Manner to Promote Lymphatic Metastasis in LUAD. IGF2BP3通过m6a依赖性方式稳定SRC RNA触发STAT3通路，促进LUAD的淋巴转移。

IF 5.7 2区医学

Cancer Science Pub Date : 2025-01-13 DOI: 10.1111/cas.16451

Jiapei Ding, Xuequan Wang, Haihua Yang, Lele Zhang, Yongquan Ying, Wenhu Pi, Guozhong Deng, Yaqun Zhu

{"title":"IGF2BP3 Triggers STAT3 Pathway by Stabilizing SRC RNA in an m6A-Dependent Manner to Promote Lymphatic Metastasis in LUAD.","authors":"Jiapei Ding, Xuequan Wang, Haihua Yang, Lele Zhang, Yongquan Ying, Wenhu Pi, Guozhong Deng, Yaqun Zhu","doi":"10.1111/cas.16451","DOIUrl":"https://doi.org/10.1111/cas.16451","url":null,"abstract":"Lymph node metastasis significantly affects the NSCLC patients' staging, treatment strategy, and prognosis. Studies have shown that IGF2BP3, an oncofetal protein and an m6A reader, overexpresses and correlates to lymph node metastasis and worse overall survival in histopathological studies including NSCLC, but its mechanism needs further study. This study explored IGF2BP3's function and mechanism in LUAD lymphatic metastasis using public databases, a human LUAD tissue microarray, human LUAD cells, and a lymphatic metastasis model in male BALB/c nude mice. Firstly, we proved that IGF2BP3 overexpression was positively correlated to patients' lymph node metastasis and worse overall survival in bioinformatics and a human LUAD tissue microarray analysis. IGF2BP3 was knocked out or overexpressed in human LUAD cell lines. Functionally, IGF2BP3 facilitated NCI-H1299, NCI-H358, and A549 cell growth, migration, invasion, and EMT in vitro, and promoted tumorigenesis, lymphangiogenesis, and lymphatic metastasis of NCI-H1299 cells in BALB/c nude mice. Mechanically, RIP, RNA pull-down assay, MeRIP, mRNA stability assays, rescue experiments, and immunohistochemical assays were conducted. IGF2BP3 was demonstrated to bind to the m6A site of the 3'UTR region of SRC, stabilizing its mRNA and activating the downstream STAT3 signaling pathway and lymphatic growth factors such as VEGF-C, therefore affecting lymphatic metastasis. The cell migration and EMT function of IGF2BP3 were partially rescued by utilizing SRC siRNA or AZD0530, an SRC inhibitor. This study demonstrated that IGF2BP3 promotes lymphatic metastasis in LUAD via activating the m6A-SRC-STAT3-VEGFC signaling axis, indicating that IGF2BP3 is a potential therapeutic target to overcome metastasis in LUAD patients.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Comparison of ¹¹C-Acetate and ¹⁸F-FDG PET/CT for Immune Infiltration and Prognosis in Hepatocellular Carcinoma. 11C-Acetate与18F-FDG PET/CT对肝细胞癌免疫浸润及预后的比较

IF 5.7 2区医学

Cancer Science Pub Date : 2025-01-11 DOI: 10.1111/cas.16449

Hao Xu, Hao Wang, Dong-Lang Jiang, Yan-Fei Wu, Sun-Zhe Xie, Ying-Han Su, Yi-Hui Guan, Fang Xie, Wen-Wei Zhu, Lun-Xiu Qin

{"title":"Comparison of 11C-Acetate and 18F-FDG PET/CT for Immune Infiltration and Prognosis in Hepatocellular Carcinoma.","authors":"Hao Xu, Hao Wang, Dong-Lang Jiang, Yan-Fei Wu, Sun-Zhe Xie, Ying-Han Su, Yi-Hui Guan, Fang Xie, Wen-Wei Zhu, Lun-Xiu Qin","doi":"10.1111/cas.16449","DOIUrl":"https://doi.org/10.1111/cas.16449","url":null,"abstract":"Immunotherapy has revolutionized cancer treatment, making it a challenge to noninvasively monitor immune infiltration. Metabolic reprogramming in cancers, including hepatocellular carcinoma (HCC), is closely linked to immune status. In this study, we aimed to evaluate the ability of carbon-11 acetate (11C-acetate) and fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT findings in predicting overall survival (OS) and immune infiltration in HCC patients. Totally 32 patients who underwent preoperative 18F-FDG and 11C-acetate PET/CT, followed by liver resection for HCC, were prospectively enrolled at authors' institute between January 2019 and October 2021. Tracer uptake was qualified. Densities of CD3+, CD8+, and granzyme B+ CD8+ immune cells were assessed and the Immunoscore was defined by combining the densities of CD3+ and CD8+ in tumor interior (TI) and invasion margin (IM). Patients with avid HCCs in 11C-acetate PET/CT demonstrated a longer OS. Those with only 11C-acetate-avid HCCs exhibited a longer OS compared to those with only 18F-FDG uptake. In contrast to 18F-FDG uptake, 11C-acetate uptake was positively associated with CD3+, CD8+, and granzyme B+ CD8+ cell infiltration. Patients with a higher Immunoscore exhibited a longer OS and an increased uptake of 11C-acetate rather than 18F-FDG. The sensitivity of 11C-acetate PET/CT in the detection of patients with immune infiltration was superior to that of 18F-FDG PET/CT (88% [21 of 24] vs. 58% [14 of 24]). These data show that preoperative 11C-acetate PET/CT may be a promising approach for the evaluation of immune status and postoperative outcome of HCCs.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Identification of clinicopathological-specific driver gene and genetic subtyping of colorectal cancer. 结直肠癌临床病理特异性驱动基因的鉴定及遗传分型。

IF 5.7 2区医学

Cancer Science Pub Date : 2025-01-11 DOI: 10.1111/cas.16432

Jianjiong Li, Chunnian Wang, Changshun Yang, Hua Bao, Ningyou Li, Xianqiang Huang, Wei Gong, Xinyue Hong, Jiani C Yin, Jiaohui Pang, Meifu Gan, Danping Yuan

{"title":"Identification of clinicopathological-specific driver gene and genetic subtyping of colorectal cancer.","authors":"Jianjiong Li, Chunnian Wang, Changshun Yang, Hua Bao, Ningyou Li, Xianqiang Huang, Wei Gong, Xinyue Hong, Jiani C Yin, Jiaohui Pang, Meifu Gan, Danping Yuan","doi":"10.1111/cas.16432","DOIUrl":"https://doi.org/10.1111/cas.16432","url":null,"abstract":"This study analyzed targeted sequencing data from 6530 tissue samples from patients with metastatic Chinese colorectal cancer (CRC) to identify low mutation frequency and subgroup-specific driver genes, using three algorithms for overall CRC as well as across different clinicopathological subgroups. We analyzed 425 cancer-related genes, identifying 101 potential driver genes, including 36 novel to CRC. Notably, some genes demonstrated subgroup specificity; for instance, ERBB4 was found as a male-specific driver gene and mutations of ERBB4 only influenced the prognosis of male patients with CRC. This sex disparity of ERBB4 was validated in an independent large-scale Memorial Sloan Kettering Cancer Center CRC cohort with 2444 samples. Furthermore, using network-based stratification based on protein-protein interaction, we classified the microsatellite stable (MSS) and unstable (MSI) CRCs into six and three major subtypes, respectively, each showing unique phenotypes and prognoses. In MSS CRC, cluster 5 (APCAMER1-KRAS) and cluster 2 (RNF43-BRAF-PIK3CA) were predominant, and cluster 5 showed a superior overall survival compared with cluster 2. This extensive heterogeneity in driver gene mutations underscores the complexity of CRC and suggests significant implications for treatment and prognostic assessments.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

LHPP-P38 MAPK/ERK-ETS1 Axis Negative Feedback Signaling Restrains Progression in Breast Cancer. LHPP-P38 MAPK/ERK-ETS1轴负反馈信号抑制乳腺癌进展

IF 5.7 2区医学

Cancer Science Pub Date : 2025-01-10 DOI: 10.1111/cas.16448

Xu Liu, Deyang Yu, Zhen Yu, Sisi Su, Meixia Jiang, Chunbo Zhao

引用次数: 0

AURKA/PLK1/CDC25C Axis as a Novel Therapeutic Target in INI1-Deficient Epithelioid Sarcoma. AURKA/PLK1/CDC25C轴作为ini1缺陷上皮样肉瘤的新治疗靶点

IF 5.7 2区医学

Cancer Science Pub Date : 2025-01-09 DOI: 10.1111/cas.16438

Akitomo Inoue, Hidetatsu Outani, Yoshinori Imura, Sho Nakai, Haruna Takami, Yuki Kotani, Hirokazu Mae, Seiji Okada

{"title":"AURKA/PLK1/CDC25C Axis as a Novel Therapeutic Target in INI1-Deficient Epithelioid Sarcoma.","authors":"Akitomo Inoue, Hidetatsu Outani, Yoshinori Imura, Sho Nakai, Haruna Takami, Yuki Kotani, Hirokazu Mae, Seiji Okada","doi":"10.1111/cas.16438","DOIUrl":"https://doi.org/10.1111/cas.16438","url":null,"abstract":"Effective therapeutic strategies for epithelioid sarcoma (EpS), a high-grade soft tissue sarcoma characterized by loss of integrase interactor 1 (INI1), have not yet been developed. The present study therefore investigated the association between INI1 loss and upregulation of the aurora kinase A (AURKA)/polo-like kinase 1 (PLK1)/cell division cycle 25C (CDC25C) axis, as well as the therapeutic relevance of this axis in EpS. Notably, our findings showed that the reintroduction of INI1 in VA-ES-BJ cells significantly reduced proliferation, mitigated tumorigenicity, and negatively regulated the expression of AURKA and its downstream effectors, as well as the activation of PLK1 and CDC25C. These results suggest that INI1 deficiency enhanced EpS growth by upregulating the AURKA/PLK1/CDC25C axis. AURKA silencing using siRNAs inhibited VA-ES-BJ and Asra-EPS cell proliferation by inactivating PLK1 and CDC25C. Alisertib, a selective AURKA inhibitor, exerted markedly greater antiproliferative effects on EpS cells than on normal human dermal fibroblasts, and these effects were dependent on INI1 deficiency. Inhibition of AURKA activity by alisertib induced G2/M cell cycle arrest and apoptosis via the inactivation of AURKA downstream effectors in EpS cells. Alisertib also significantly decreased VA-ES-BJ xenograft tumor growth. Taken together, our findings revealed that INI1 loss in EpS cells enhances the expression of AURKA and its downstream effectors and persistently activates PLK1 and CDC25C mediated by AURKA, making the cells reliant on the AURKA/PLK1/CDC25C axis. Therefore, the AURKA/PLK1/CDC25C axis activated by INI1 deficiency could serve as a novel therapeutic target for this devastating disease.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

CYP24A1 Binding to FUS Maintains Tumor Properties by Regulating the miR-200c/ZEB1/EMT Axis. CYP24A1结合FUS通过调节miR-200c/ZEB1/EMT轴维持肿瘤特性。

IF 5.7 2区医学

Cancer Science Pub Date : 2025-01-07 DOI: 10.1111/cas.16445

Ping Wang, Jiming Xu, Weijing You, Jie Li, Jing Yu, Fei Jiang, Zengli Zhang, Wentao Hu, Bingyan Li

{"title":"CYP24A1 Binding to FUS Maintains Tumor Properties by Regulating the miR-200c/ZEB1/EMT Axis.","authors":"Ping Wang, Jiming Xu, Weijing You, Jie Li, Jing Yu, Fei Jiang, Zengli Zhang, Wentao Hu, Bingyan Li","doi":"10.1111/cas.16445","DOIUrl":"https://doi.org/10.1111/cas.16445","url":null,"abstract":"The active vitamin D-degrading enzyme (CYP24A1) is commonly overexpressed in various types of cancer, which is associated with poor prognosis in cancer patients. Recent studies highlight the antagonism of CYP24A1 toward the anticancer role of active vitamin D. However, the impact of CYP24A1 on tumorigenesis and its underlying mechanisms largely remains unexplored. This study also found that high CYP24A1 mRNA expressions were associated with poor prognosis in ovarian cancer and lung adenocarcinoma (LUAD) patients. Moreover, we demonstrated that the overexpression of CYP24A1 accelerated the proliferation, migration, and invasion of ovarian cancer and LUAD cancer cells in vitro. Furthermore, knockdown of CYP24A1 displayed an anticancer effector both in vitro and in vivo. Mechanically, 87-297 amino acid motif of CYP24A1 bound specifically to FUS protein, consequentially reducing FUS affinity for miR-200c. Considering FUS promotes gene silencing by binding to microRNA targets, a decrease in miR-200c levels led to a notable activation of its target ZEB1, resulting in the promotion of the epithelial-mesenchymal transition (EMT) process. In conclusion, FUS binding specifically by CYP24A1 impaired miR-200c-mediated ZEB1 silencing, thereby augmenting EMT progression and tumorigenesis. These findings elucidate a fundamental mechanism by which CYP24A1 operates as an oncogene, offering potential targets for therapeutic interventions in cancer treatment.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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