Xiao-Mei Rao, Michael T. Tseng, Xinyu Zheng, Yanbin Dong, Azemat Jamshidi-Parsian, Timothy C. Thompson, Malcolm K. Brenner, Kelly M. McMasters, Heshan Sam Zhou
{"title":"Editorial Expression of Concern: E1A-induced apoptosis does not prevent replication of adenoviruses with deletion of E1b in majority of infected cancer cells","authors":"Xiao-Mei Rao, Michael T. Tseng, Xinyu Zheng, Yanbin Dong, Azemat Jamshidi-Parsian, Timothy C. Thompson, Malcolm K. Brenner, Kelly M. McMasters, Heshan Sam Zhou","doi":"10.1038/s41417-024-00860-x","DOIUrl":"10.1038/s41417-024-00860-x","url":null,"abstract":"","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 1","pages":"147-147"},"PeriodicalIF":4.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00860-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779386","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}
Darshini Kuruppu, Deepak Bhere, Christian T. Farrar, Khalid Shah, Anna-Liisa Brownell, Kenneth K. Tanabe
{"title":"Correction: A model of breast cancer meningeal metastases: characterization with in vivo molecular imaging","authors":"Darshini Kuruppu, Deepak Bhere, Christian T. Farrar, Khalid Shah, Anna-Liisa Brownell, Kenneth K. Tanabe","doi":"10.1038/s41417-024-00800-9","DOIUrl":"10.1038/s41417-024-00800-9","url":null,"abstract":"","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 12","pages":"1895-1895"},"PeriodicalIF":4.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00800-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724637","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}
{"title":"CCDC34 maintains stemness phenotype through β-catenin-mediated autophagy and promotes EGFR-TKI resistance in lung adenocarcinoma","authors":"Ping Yue, Yuchao He, Ran Zuo, Wenchen Gong, Yu Wang, Liwei Chen, Yi Luo, Yuanying Feng, Yuan Gao, Zhiyong Liu, Peng Chen, Hua Guo","doi":"10.1038/s41417-024-00843-y","DOIUrl":"10.1038/s41417-024-00843-y","url":null,"abstract":"Despite recent advances in treatment strategy, lung cancer remains the leading cause of cancer-related mortality worldwide, and it is a serious threat to human health. Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer, and approximately 40–50% of patients with LUAD in Asian populations have epidermal growth factor receptor (EGFR) mutations. The use of EGFR tyrosine kinase inhibitors (EGFR-TKIs) has revolutionarily improved the prognosis of patients with EGFR-mutated LUAD. However, acquired drug resistance is the main cause of treatment failure. Therefore, new therapeutic strategies are necessary to address the resistance to EGFR-TKIs in patients with LUAD. Cancer stemness-related factors lead to multiple-drug resistance in cancer treatment, including EGFR–TKI resistance. Coiled-coil domain-containing 34 (CCDC34) serves as an oncogene in several types of cancer. However, the role and molecular mechanism of CCDC34 in the malignant progression of LUAD have not been reported to date. In the present study, we found that CCDC34 may be associated with LUAD stemness through weighted gene co-expression network analysis (WGCNA). Furthermore, we demonstrated that CCDC34 promoted LUAD stemness properties through β-catenin-mediated regulation of ATG5-induced autophagy, which was conducive to acquired EGFR-TKI resistance in LUAD in vitro and in vivo. Knockdown CCDC34 can synergistically inhibit tumor growth when combined with EGFR-TKIs. This study reveals a positive association between CCDC34 and the stemness phenotype of LUAD, providing new insights into overcoming EGFR-TKI resistance in LUAD by inhibiting CCDC34 expression.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 1","pages":"104-121"},"PeriodicalIF":4.8,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715498","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}
Maxim E. Menyailo, Elena E. Kopantseva, Anna A. Khozyainova, Anastasia A. Korobeynikova, Evgeny V. Denisov
{"title":"Soft tissue sarcomas at the single-cell and spatial resolution: new markers and targets","authors":"Maxim E. Menyailo, Elena E. Kopantseva, Anna A. Khozyainova, Anastasia A. Korobeynikova, Evgeny V. Denisov","doi":"10.1038/s41417-024-00856-7","DOIUrl":"10.1038/s41417-024-00856-7","url":null,"abstract":"Soft tissue sarcomas (STS) are heterogeneous and aggressive tumors, originating in connective tissues embryologically derived from the mesenchyme. Due to their rarity, crucial information about their biology is still lacking. In recent years, single-cell and spatial analyses have opened up new horizons in oncology, leading to the possibility of characterizing the internal architecture of the tumor at the single-cell and spatial levels. This review summarizes the first results acquired through these revolutionary methods for different types of STS. We discuss tumor cell populations and their evolution, interactions between tumor cells and the microenvironment, new prognostic markers, and clinically important targets. Finally, we examine the challenges presented by the single-cell and spatial omics of STS and the future perspectives in this field.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 1","pages":"11-21"},"PeriodicalIF":4.8,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00856-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709170","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}
{"title":"Establishment and characterization of the first immortalized vocal cord leukoplakia epithelial cell line","authors":"Zi-Ming Fu, Yang-Yang Bao, Zhe Chen, Jiang-Tao Zhong, Heng-Chao Chen, Zai-Zai Cao, Shui-Hong Zhou","doi":"10.1038/s41417-024-00859-4","DOIUrl":"10.1038/s41417-024-00859-4","url":null,"abstract":"The importance of vocal cord leukoplakia (VCL) in the etiology and progression of laryngeal carcinoma has gained increasing recognition. However, research into the mechanisms of laryngeal precancerous lesions such as VCL, has been hampered by the small size of VCL epithelial cells and their limited culture lifespan. In this study, we enhanced the primary culture protocol for VCL epithelial cells and introduced simian virus 40 Large T to establish an immortalized cell line, designated hVCL-MSDEP01. We confirmed that hVCL-MSDEP01 expresses epithelial-specific genes and proteins; it also demonstrates distinct cell cycle dynamics and apoptosis rates compared with primary cells. In conclusion, hVCL-MSDEP01 serves as an ideal in vitro model for studying VCL. This cell line will substantially advance research into the etiology and progression of laryngeal carcinoma.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 1","pages":"95-103"},"PeriodicalIF":4.8,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695325","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}
Adrian Buensuceso, Matthew J. Borrelli, Yudith Ramos Valdés, Trevor G. Shepherd
{"title":"Reversible downregulation of MYC in a spheroid model of metastatic epithelial ovarian cancer","authors":"Adrian Buensuceso, Matthew J. Borrelli, Yudith Ramos Valdés, Trevor G. Shepherd","doi":"10.1038/s41417-024-00850-z","DOIUrl":"10.1038/s41417-024-00850-z","url":null,"abstract":"Upon detachment from the primary tumour, epithelial ovarian cancer cells can form multicellular aggregates, also referred to as spheroids, that have the capacity to establish metastases at distant sites. These structures exhibit numerous adaptations that may facilitate metastatic transit and promote tumorigenic potential. One such adaptation is the acquisition of dormancy, characterized by decreased proliferation and molecular features of quiescence. One of the most frequently dysregulated genes in cancer is MYC, which encodes a transcription factor that promotes cell proliferation. In this study, we demonstrate that MYC protein abundance and associated gene expression is significantly decreased in EOC spheroids compared to adherent cells. This downregulation occurs rapidly upon cell detachment and is proteasome-dependent. Moreover, MYC protein abundance and associated gene expression is restored upon spheroid reattachment to an adherent culture surface. Overall, our findings suggest that suppression of MYC activity is a common feature of EOC spheroids and may contribute to the reversible acquisition of dormancy.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 1","pages":"83-94"},"PeriodicalIF":4.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686230","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}
Kai Ye, Yongfeng Yan, Rui Su, Qinghai Dai, Kunyan Qiao, Yu Cao, Jian Xu, Lihua Yan, Zhixiao Huo, Wei Liu, Yue Hu, Yu Zhu, Liang Xu, Yuqiang Mi
{"title":"Oncolytic virus encoding 4-1BBL and IL15 enhances the efficacy of tumor-infiltrating lymphocyte adoptive therapy in HCC","authors":"Kai Ye, Yongfeng Yan, Rui Su, Qinghai Dai, Kunyan Qiao, Yu Cao, Jian Xu, Lihua Yan, Zhixiao Huo, Wei Liu, Yue Hu, Yu Zhu, Liang Xu, Yuqiang Mi","doi":"10.1038/s41417-024-00853-w","DOIUrl":"10.1038/s41417-024-00853-w","url":null,"abstract":"Previous studies have found that oncolytic virus (OVs) can improve the efficacy of TIL adoptive therapy in oral cancer, colon cancer, and pancreatic cancer. However, the curative effect in hepatocellular carcinoma (HCC) is still unclear. Therefore, this study aims to explore the therapeutic effect and mechanism of OVs encoding 4-1BBL and IL15 (OV-4-1BBL/IL15) combined with TIL adoptive therapy on HCC. In this study, the role and immunological mechanism of armed OVs combined with TILs were evaluated by flow cytometry and ELISA in patient-derived xenograft and syngeneic mouse tumor models. Co-culturing with TILs can up-regulate the expression of antigen-presenting cell (APC) markers on the surface of OV-infected primary HCC cells, and promote the specific activation ability and tumor-killing ability of TILs. OV-4-1BBL/IL15 combined with TIL adoptive therapy could induce tumor volume reduction and anti-tumor immune memory in patient-derived xenograft and syngeneic mouse tumor models. Furthermore, OV combined with TIL adoptive therapy can endow tumor cells with aAPC characteristics, activate T cells at the same time, and reprogram tumor macrophages into anti-tumor phenotype. OV-4-1BBL/IL15 can stimulate the anti-tumor potential of TIL therapy in HCC, and possess broad clinical application prospects.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 1","pages":"71-82"},"PeriodicalIF":4.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00853-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680975","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}
Huitong Bu, Chaozhu Pei, Min Ouyang, Yan Chen, Li Yu, Xiaoqin Huang, Yongjun Tan
{"title":"The antitumor peptide M1-20 induced the degradation of CDK1 through CUL4-DDB1-DCAF1-involved ubiquitination","authors":"Huitong Bu, Chaozhu Pei, Min Ouyang, Yan Chen, Li Yu, Xiaoqin Huang, Yongjun Tan","doi":"10.1038/s41417-024-00855-8","DOIUrl":"10.1038/s41417-024-00855-8","url":null,"abstract":"CDK1 is an oncogenic serine/threonine kinase known to play an important role in the regulation of the cell cycle. FOXM1, as one of the CDK1 substrates, requires binding of CDK1/CCNB1 complex for phosphorylation-dependent recruitment of p300/CBP coactivators to mediate transcriptional activity. Previous studies from our laboratory found that a novel peptide (M1-20) derived from the C-terminus of FOXM1 exhibited potent inhibitory effects for cancer cells. Based on these proofs and to explore the inhibitory mechanism of M1-20, we designed experiments and found that CDK1 served as an important target of M1-20. M1-20 enhanced the ubiquitination and degradation of CDK1 by CUL4-DDB1-DCAF1 complexes through the proteasome pathway. M1-20 could also affect the formation of CDK1/CCNB1 complexes. In addition, compared to RO3306, a CDK1 inhibitor, M1-20 exhibited excellent inhibitory effects in FVB/N MMTV-PyVT murine model of spontaneous breast cancer. These results suggested that M1-20 was a potential CDK1 inhibitor for the treatment of cancer.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 1","pages":"61-70"},"PeriodicalIF":4.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675168","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}
{"title":"CEACAM6 facilitates gastric cancer progression through upregulating SLC27A2","authors":"Xiaqiong Mao, Tongtai Liu, Shunying Yu, Yuqi Wei, Chunli Zhou, Xiaoyi Kuai","doi":"10.1038/s41417-024-00846-9","DOIUrl":"10.1038/s41417-024-00846-9","url":null,"abstract":"Gastric cancer (GC) is one of the most lethal cancers. However, the underlying mechanisms are not yet fully understood. Here, we investigated the role of carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) in tumor initiation and progression in GC and proposed therapeutic strategies for CEACAM6-positive patients. In this article, we found that CEACAM6 overexpression promoted GC initiation and progression by overactivating FAO. CEACAM6 promotes SLC27A2 expression, contributing to enhanced fatty acid incorporation. CEACAM6 interacts with both SLC27A2 and USP29, facilitating the deubiquitination of USP29 on SLC27A2. Pharmacological inhibition of SLC27A2 attenuates the tumor-initiating ability of GC. Taken together, CEACAM6 overexpression facilitates GC progression by upregulating fatty acid uptake through SLC27A2, thereby contributing to FAO. Genetic ablation of SLC27A2 is a promising therapeutic strategy for patients with CEACAM6-positive GC.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 1","pages":"51-60"},"PeriodicalIF":4.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675103","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}