Article
Medicine, General & Internal
Ombline de Calbiac, Amelie Lusque, Audrey Mailliez, Thomas Bachelot, Lionel Uwer, Marie-Ange Mouret-Reynier, George Emile, Christelle Jouannaud, Anthony Goncalves, Anne Patsouris, Veronique Dieras, Marianne Leheurteur, Thierry Petit, Paul Cottu, Jean-Marc Ferrero, Veronique D'Hondt, Isabelle Desmoulins, Joana Mourato-Ribeiro, Anne-Laure Martin, Jean-Sebastien Frenel
Summary: In a study of breast cancer patients, it was found that patients with ERBB2-low expression had slightly better overall survival compared to those with completely ERBB2-zero tumors, but identical progression-free survival under first-line treatments, which could help with treatment selection.
Article
Biochemistry & Molecular Biology
Xiaosong Hu, Ruochen Liu, Jianbing Hou, Wen Peng, Sicheng Wan, Minghao Xu, Yongsen Li, Guanghui Zhang, Xuan Zhai, Ping Liang, Hongjuan Cui
Summary: This study reveals the critical oncogenic role of SMARCE1 gene in neuroblastoma, particularly in cases with MYCN amplification. SMARCE1 interacts with MYCN to mediate transcriptional activation of downstream target genes, promoting neuroblastoma proliferation and tumorigenicity. These findings provide a new potential therapeutic target for neuroblastoma with 17q21-ter gain and MYCN amplification.
Editorial Material
Cell Biology
Mingang Hao, Syn Kok Yeo, Jun-Lin Guan
Summary: Autophagy inhibition can effectively prevent the occurrence of ERBB2-driven breast tumors, with stronger effects than previous studies using other models. Autophagy inhibition disrupts intracellular trafficking of ERBB2 and triggers its release via extracellular vesicles.
Article
Cell Biology
Dan Li, Mingjun San, Jing Zhang, Anlan Yang, Wanhua Xie, Yang Chen, Xiaodan Lu, Yuntao Zhang, Mingyue Zhao, Xuechao Feng, Yaowu Zheng
Summary: The study using a transgenic mouse model of OXTR overexpression found that OXTR can promote mammary hyperplasia and tumorigenesis, as well as creating a microenvironment that promotes tumor growth, providing potential for targeted therapy in HER2-type breast cancer.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Hui Pan, Huixue Wang, Xiaoyu Zhang, Fan Yang, Xianqun Fan, He Zhang
Summary: This study identifies a CNV-induced lncRNA, MAT1, that plays an oncogenic role in promoting tumorigenesis of uveal melanoma. MAT1 interrupts the interaction between the MLL1 complex and the PCDH20 promoter, leading to the abolishment of H3K4 trimethylation and inactivation of tumor suppressor PCDH20 transcription, thereby accelerating tumorigenesis.
Article
Multidisciplinary Sciences
Gerda Kildisiute, Waleed M. Kholosy, Matthew D. Young, Kenny Roberts, Rasa Elmentaite, Sander R. van Hooff, Clarissa N. Pacyna, Eleonora Khabirova, Alice Piapi, Christine Thevanesan, Eva Bugallo-Blanco, Christina Burke, Lira Mamanova, Kaylee M. Keller, Karin P. S. Langenberg-Ververgaert, Philip Lijnzaad, Thanasis Margaritis, Frank C. P. Holstege, Michelle L. Tas, Marc H. W. A. Wijnen, Max M. van Noesel, Ignacio Del Valle, Giuseppe Barone, Reinier van der Linden, Catriona Duncan, John Anderson, John C. Achermann, Muzlifah Haniffa, Sarah A. Teichmann, Dyanne Rampling, Neil J. Sebire, Xiaoling He, Ronald R. de Krijger, Roger A. Barker, Kerstin B. Meyer, Omer Bayraktar, Karin Straathof, Jan J. Molenaar, Sam Behjati
Summary: The neuroblastoma cancer cells resemble fetal sympathoblasts, indicating a pan-neuroblastoma cancer cell state that could potentially be targeted for novel treatment strategies. The findings highlight the importance of understanding the phenotype of neuroblastoma cells for the development of immunotherapeutic and targeted avenues.
Article
Multidisciplinary Sciences
Gao Sheng, Hongyan Yuan, Lu Jin, Suman Ranjit, Julia Panov, Xun Lu, Moshe Levi, Robert I. Glazer
Summary: The study identified fibrosis as a crucial factor in tumor progression, and demonstrated that using the LXR agonist DMHCA could reduce fibrosis, improve immune surveillance, decrease tumor progression and enhance the efficacy of cancer therapy.
Article
Biochemical Research Methods
Daniel Schwabe, Martin Falcke
Summary: This study establishes a single-cell RNA sequencing model to investigate the impact of technical noise on the relationship between output distribution and cellular distribution. Exact expressions for copy number distribution of single transcripts during PCR amplification are provided.
Article
Cell Biology
Tao Wei, Jin Li, Jian Zhang, Qi Zhang, Xiaoyu Liu, Qi Chen, Liang Wen, Ke Ma, Wen Chen, Jianhui Zhao, Cheng Zhang, Jinyan Huang, Yali Xie, Hao Qin, Danfeng Qian, Tingbo Liang
Summary: While Mettl3 has been shown to have oncogenic roles in hepatocellular carcinoma (HCC), its function in early HCC tumorigenesis is unclear. Mettl3 loss leads to hepatocyte homeostasis disruption and liver damage, accelerating liver tumorigenesis. Depletion of Mettl3 enhances liver tumor development, while overexpression of Mettl3 inhibits hepatocarcinogenesis. These findings suggest a stage-dependent tumor-suppressive role of Mettl3 in HCC initiation and progression.
Article
Oncology
Chunluan Yuan, Yue Ding, Yan Zhuang, Chongguo Zhang, Liang Han, Wei Li, Renhua Guo, Erbao Zhang
Summary: Recent studies have shown that lncRNAs, such as LINC00662, play significant roles in the regulation of cancer cells proliferation, apoptosis, and metastasis. This study identified LINC00662 as a long noncoding RNA with high copy number amplification in NSCLC, and its high expression was associated with poor survival. Mechanistically, LINC00662 was found to interact with EZH2 and recruit it to the promoter regions of BIK, leading to epigenetic repression of BIK expression and promotion of tumorigenesis in lung cancer cells.
Article
Medicine, Research & Experimental
Thanh H. Nguyen, Prasantha L. Vemu, Gregory E. Hoy, Salah Boudjadi, Bishwanath Chatterjee, Jack F. Shern, Javed Khan, Wenyue Sun, Frederic G. Barr
Summary: Comparative analysis revealed the importance of SHMT2 in tumorigenesis of FP RMS, and SHMT2 amplification can predict differential response to drugs targeting this metabolic pathway.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Alexandra M. Simond, Tung Bui, Dongmei Zuo, Virginie Sanguin-Gendreau, Trisha Rao, Wayne A. Phillips, Robert D. Cardiff, William J. Muller
Summary: This study found that the p110 alpha(HR) mutation attenuates metastatic behavior and is associated with the formation of ductal carcinoma in situ (DCIS) in ErbB2-driven breast cancer.
Article
Cell Biology
Dong Hoon Lee, Go Woon Kim, Jung Yoo, Sang Wu Lee, Yu Hyun Jeon, So Yeon Kim, Hyeok Gu Kang, Da-Hyun Kim, Kyung-Hee Chun, Junjeong Choi, So Hee Kwon
Summary: The study reveals the crucial role of KDM4C in glioblastoma, showing that its inhibition can effectively suppress tumor proliferation and formation. KDM4C modulates tumor cell growth and apoptosis by demethylating p53 and activating c-Myc in glioblastoma cells.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Sun Hee Lee, Do Young Hyeon, Soo-Hyun Yoon, Ji-Hak Jeong, Saeng-Myung Han, Ju-Won Jang, Minh Phuong Nguyen, Xin-Zi Chi, Sojin An, Kyung-gi Hyun, Hee-Jung Jung, Ji-Joon Song, Suk-Chul Bae, Woo-Ho Kim, Daehee Hwang, You Mie Lee
Summary: Under hypoxic conditions, G9a-mediated methylation regulates the inactivation of RUNX3, promoting cancer cell proliferation and suppressing immune response and apoptosis, thereby facilitating tumor growth during early tumorigenesis.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Cell Biology
Binbin Chen, Huimou Chen, Suying Lu, Xiaoqin Zhu, Yi Que, Yu Zhang, Junting Huang, Li Zhang, Yu Zhang, Feifei Sun, Juan Wang, Jia Zhu, Zijun Zhen, Yizhuo Zhang
Summary: Upregulated histone demethylase KDM5B in Ewing sarcoma (EwS) was found to be associated with poor prognosis. KDM5B is involved in regulating the cell cycle pathway and affects the accumulation of CCNE1 protein. Targeting KDM5B with epigenetic drugs could be a potential treatment for EwS.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Makoto Saito, Daniel Hess, Jan Eglinger, Anatol W. Fritsch, Moritz Kreysing, Brian T. Weinert, Chunaram Choudhary, Patrick Matthias
NATURE CHEMICAL BIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Kseniya Ustinova, Zora Novakova, Makoto Saito, Marat Meleshin, Jana Mikesova, Zsofia Kutil, Petra Baranova, Barbora Havlinova, Mike Schutkowski, Patrick Matthias, Cyril Barinka
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Letter
Medicine, General & Internal
Julia Joung, Alim Ladha, Makoto Saito, Nam-Gyun Kim, Ann E. Woolley, Michael Segel, Robert P. J. Barretto, Amardeep Ranu, Rhiannon K. Macrae, Guilhem Faure, Eleonora I. Ioannidi, Rohan N. Krajeski, Robert Bruneau, Meei-Li W. Huang, Xu G. Yu, Jonathan Z. Li, Bruce D. Walker, Deborah T. Hung, Alexander L. Greninger, Keith R. Jerome, Jonathan S. Gootenberg, Omar O. Abudayyeh, Feng Zhang
NEW ENGLAND JOURNAL OF MEDICINE
(2020)
Article
Biochemistry & Molecular Biology
Makoto Saito, Alim Ladha, Jonathan Strecker, Guilhem Faure, Edwin Neumann, Han Altae-Tran, Rhiannon K. Macrae, Feng Zhang
Summary: Tn7-like transposons have incorporated CRISPR systems, including different types such as I-F, I-B, and V-K. Despite being guided by CRISPR RNA, CASTs are rarely found in sites targeted by the cognate CRISPR array's crRNAs. Through studying V-K and I-B systems, researchers have identified two distinct modes of transposition: crRNA-guided and CRISPR array-independent homing, each utilizing different molecular mechanisms for targeting their homing site. These findings shed light on the diverse molecular mechanisms mediating transposon homing within CAST systems.
Article
Multidisciplinary Sciences
Honami Miyakura, Mei Fukuda, Hiroya Enomoto, Kosuke Ishikawa, Shinya Watanabe, Kentaro Semba
Summary: A new screening system combining BiFC and a transposon gene trap system was established for identifying interacting proteins. This system successfully identified several interactors of the NF-kappa B subunit p65, including PKM, HSP90AB1, ANXA2, HSPA8, and CACYBP, with CACYBP enhancing NF-kappa B reporter activation under TNF alpha stimulation. This screening system provides a valuable method for identifying interacting factors not identified by other methods.
Article
Multidisciplinary Sciences
Makoto Saito, Yasushi Itoh, Fumihiko Yasui, Tsubasa Munakata, Daisuke Yamane, Makoto Ozawa, Risa Ito, Takayuki Katoh, Hirohito Ishigaki, Misako Nakayama, Shintaro Shichinohe, Kenzaburo Yamaji, Naoki Yamamoto, Ai Ikejiri, Tomoko Honda, Takahiro Sanada, Yoshihiro Sakoda, Hiroshi Kida, Thi Quynh Mai Le, Yoshihiro Kawaoka, Kazumasa Ogasawara, Kyoko Tsukiyama-Kohara, Hiroaki Suga, Michinori Kohara
Summary: Researchers have developed a class of macrocyclic peptides named iHA, which can bind the influenza viral envelope protein hemagglutinin and inhibit virus infection by blocking adsorption and fusion. Particularly, iHA-100 shows powerful efficacy in inhibiting the growth of highly pathogenic influenza viruses and preventing severe pneumonia at later stages of infection in mouse and non-human primate cynomolgus macaque models, indicating its potential as a next-generation, mid-sized biomolecule.
NATURE COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Kosuke Ishikawa, Sakura Tamamura, Kentaro Semba, Shinya Watanabe
Summary: By screening reporter cells under specific conditions, the study identified PKP2 as a novel gene responding to glucocorticoids, potentially supplementing the current GRE-based reporter systems. Due to differences in responses to steroids among different clones, using these clones can provide more information.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Kosuke Ishikawa, Sakura Tamamura, Nobuhito Takahashi, Motoki Takagi, Kentaro Semba, Shinya Watanabe
Summary: This study established a promoter-trapping vector system using the piggyBac transposon and successfully isolated reporter cells responsive to vitamin A and vitamin D. Several new responsive genes were identified, and the study demonstrated the efficient identification of novel genes with unusual characteristics using random screening. The findings suggest the potential application of similar approaches for identifying new markers and analyzing nutrients, toxins, and metabolites.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Megumi Aoyama, Kosuke Ishikawa, Shuntaro Nemoto, Hiroyuki Hirano, Nobumoto Watanabe, Hiroyuki Osada, Shinya Watanabe, Kentaro Semba
Summary: This study establishes a system to evaluate the cancer-inhibitory activity of surrounding nontransformed cells and identifies lonidamine and domperidone as compounds that can inhibit the expansion of oncogenic foci. The findings suggest that these compounds suppress the movement of nontransformed cells and promote stress fiber formation, potentially leading to the development of a new type of drug that induces the anticancer activity of surrounding non-transformed cells.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Guilhem Faure, Makoto Saito, Sean Benler, Iris Peng, Yuri I. Wolf, Jonathan Strecker, Han Altae-Tran, Edwin Neumann, David Li, Kira S. Makarova, Rhiannon K. Macrae, Eugene V. Koonin, Feng Zhang
Summary: In order to spread, transposons need to integrate into target sites without disrupting essential genes and avoid being detected by host defense systems. Tn7-like transposons use various mechanisms, such as protein-guided or RNA-guided targeting, to select target sites. Through phylogenomic and structural analyses, researchers discovered different target-selector proteins used by Tn7 to recognize target sites, including previously unknown ones found in newly discovered transposable elements (TEs). The study also experimentally characterized a CAST I-D system and a Tn6022-like transposon, uncovering the role of TnsF in targeting the comM gene, and identified a nonTn7 transposon, Tsy, that inserts into comM using a homolog of TnsF with an active tyrosine recombinase domain. These findings highlight the modular architecture of Tn7 transposons and their ability to adapt target selectors from various sources to optimize target selection and facilitate transposon spread.
Article
Multidisciplinary Sciences
Joseph Kreitz, Mirco J. J. Friedrich, Akash Guru, Blake Lash, Makoto Saito, Rhiannon K. K. Macrae, Feng Zhang
Summary: Researchers discovered a type of bacteria called Photorhabdus that has a unique delivery system, allowing it to inject protein payloads into host cells. This system can be reprogrammed to target different organisms, including human cells, and has potential applications in gene therapy, cancer treatment, and biocontrol.
Article
Multidisciplinary Sciences
Makoto Saito, Peiyu Xu, Guilhem Faure, Samantha Maguire, Soumya Kannan, Han Altae-Tran, Sam Vo, AnAn Desimone, Rhiannon K. K. Macrae, Feng Zhang
Summary: RNA-guided systems play a central role in biological processes and provide adaptive immunity against foreign genetic elements. Recently, a new class of prokaryotic RNA-guided systems called OMEGA has been discovered, which includes the RNA-guided endonuclease TnpB. This study characterizes Fz, a eukaryotic OMEGA system, and demonstrates its potential for genome engineering applications in humans. The structure of Spizellomyces punctatus Fz is also resolved, revealing the conservation of core regions among Fz, TnpB, and Cas12.
Article
Oncology
Ziyu Liu, Akiko Okano, Emiko Sanada, Yushi Futamura, Toshihiko Nogawa, Kosuke Ishikawa, Kentaro Semba, Jiang Li, Xiaomeng Li, Hiroyuki Osada, Nobumoto Watanabe
Summary: In this study, a screening strategy was established to identify natural products as potential c-Myc inhibitors. A microbial extract from Streptomyces sp. RK19-A0402 was found to strongly inhibit c-Myc transcriptional activity. Compounds in the extract showed structural similarities to cytovaricin and oligomycin A, and inhibited mitochondrial complex V, leading to mitochondrial dysfunction and the production of reactive oxygen species (ROS). The ROS then activated GSK3α/β to phosphorylate c-Myc, promoting its ubiquitination.
Meeting Abstract
Oncology
Liu Ziyu, Kosuke Ishikawa, Kentaro Semba, Hiroyuki Osada, Nobumoto Watanabe
Article
Biology
Mizuki Yamamoto, Chiho Abe, Sakura Wakinaga, Kota Sakane, Yo Yumiketa, Yuu Taguchi, Takayuki Matsumura, Kosuke Ishikawa, Jiro Fujimoto, Kentaro Semba, Maki Miyauchi, Taishin Akiyama, Jun-ichiro Inoue
COMMUNICATIONS BIOLOGY
(2019)
