Article
Chemistry, Multidisciplinary
Qiong-Dan Hu, Hong-Lian Wang, Jian Liu, Tao He, Rui-Zhi Tan, Qiong Zhang, Hong-Wei Su, Fahsai Kantawong, Hui-Yao Lan, Li Wang
Summary: Btg2 plays a pathogenic role in FSGS by promoting podocyte injury through a Smad3-dependent epithelial-mesenchymal transition pathway.
Article
Cell Biology
Jun Zhou, Yasamin Dabiri, Rodrigo A. Gama-Brambila, Shahrouz Ghafoory, Mukaddes Altinbay, Arianeb Mehrabi, Mohammad Golriz, Biljana Blagojevic, Stefanie Reuter, Kang Han, Anna Seidel, Ivan Dikic, Stefan Wolfl, Xinlai Cheng
Summary: The study identifies pVHL as an E3 ligase for SMAD3 ubiquitination, which interacts with SMAD3 triggering its degradation, negatively regulating the TGF-beta/SMAD3 signaling pathway. Loss of pVHL in Drosophila leads to up-regulation of TGF-beta targets and a downward wing blade phenotype, rescued by inhibition of SMAD activity. The ectopic veinlets and reduced wing growth observed in Drosophila upon pVHL expression mirrors the effects seen with loss of TGF-beta/SMAD signaling.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yong Du, Chun Xie, Sneha Ravikumar, Jacob Orme, Li Li, Xin J. Zhou, Chandra Mohan
Summary: This study revealed the essential role of the TGF-beta/SMAD signaling pathway in the development of immune-mediated nephritis in 129sv mice, with Smad3 deletion ameliorating the nephritis, including crescentic glomerulonephritis. These findings suggest that SMAD3 could be a potential therapeutic target for immune-mediated nephritis in this mouse strain.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Yonghong Sun, Xingxing Chen, Lili Chen, Baixin Bao, Chunming Li, Yongning Zhou
Summary: This study identified MFAP2 as a potential target for the clinical treatment of liver fibrosis by analyzing data from gene expression databases. It was found that MFAP2 was elevated in liver fibrosis and its inhibition could attenuate HSC proliferation and fibrogenesis. In vitro experiments further demonstrated that MFAP2 inhibition alleviated hepatic fibrosis by inhibiting active HSCs activation and inducing apoptosis.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2023)
Article
Gastroenterology & Hepatology
Tsz Lam Matthew Wong, Tin-Lok Wong, Lei Zhou, Kwan Man, James Purcell, Terence K. Lee, Jing-Ping Yun, Stephanie Ma
Summary: In this study, a kinase called protein tyrosine kinase 7 (PTK7) was identified as a significantly upregulated molecule in advanced and metastatic hepatocellular carcinoma (HCC). Functional and signaling studies revealed that PTK7 can enhance the metastatic potential of HCC cells by promoting epithelial-mesenchymal transition. These findings suggest that PTK7 could be a potential target for antimetastatic therapies.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Medicine, Research & Experimental
Changsheng Huang, Fuqing Hu, Da Song, Xuling Sun, Anyi Liu, Qi Wu, Xiaowei She, Yaqi Chen, Lisheng Chen, Fayong Hu, Feng Xu, Xuelai Luo, Yongdong Feng, Xiangping Yang, Junbo Hu, Guihua Wang
Summary: This study reveals the critical role of EZH2-mediated SMAD3 K53/K333 methylation in the activation of SMAD3, which is associated with cancer metastasis and poor survival outcomes.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Oncology
Hongyi Li, Shaojie Wang, Xiubo Li, Yongjia Weng, Dinghe Guo, Pengzhou Kong, Caixia Cheng, Yanqiang Wang, Ling Zhang, Xiaolong Cheng, Yongping Cui
Summary: CDCA7 overexpression promotes the metastasis and invasion of ESCC cell lines and is associated with the expression of EMT-related markers and the TGF-beta signaling pathway. CDCA7 plays a crucial role in EMT by regulating the expression of Smad4 and Smad7 in the TGF-beta signaling pathway.
Article
Pharmacology & Pharmacy
Fangfang Cai, Huangru Xu, Daolong Zha, Xiaoyang Wang, Ping Li, Shihui Yu, Yingying Yao, Xiaoyao Chang, Jia Chen, Yanyan Lu, Zi-Chun Hua, Hongqin Zhuang
Summary: AK2 regulates tumor cell metastasis in lung adenocarcinoma, with its high expression associated with poor patient survival; AK2 is closely related to the migration and invasion ability of lung adenocarcinoma cells; AK2 may regulate epithelial-mesenchymal transition through Smad-related signaling pathways.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Oncology
Jinquan Liu, Bo Yuan, Jin Cao, Hongjie Luo, Shuchen Gu, Mengdi Zhang, Ran Ding, Long Zhang, Fangfang Zhou, Mien-Chie Hung, Pinglong Xu, Xia Lin, Jianping Jin, Xin-Hua Feng
Summary: The study identifies AMBRA1 as a novel regulator of TGF beta signaling and breast cancer metastasis, supporting further exploration of AMBRA1 as a target for cancer therapy.
Article
Pharmacology & Pharmacy
Yinhui Wang, Kun Yu, Chengcheng Zhao, Ling Zhou, Jia Cheng, Dao Wen Wang, Chunxia Zhao
Summary: The study revealed that Follistatin plays a cardioprotective role in attenuating diabetic cardiomyopathy by reducing cardiac fibrosis and reactive oxygen species production, and enhancing matrix metallopeptidase 9 activities.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Lu Liu, Qiqi Li, Liu Yang, Qifa Li, Xing Du
Summary: The study illustrates a novel mechanism in which SMAD4, as the only Co-SMAD, positively regulates the canonical TGF-beta family signaling pathways in granulosa cells (GCs) by interacting with the core promoters of upstream receptors through the recruitment of three coactivators (c-JUN, CREB1, and SP1). Different interaction modes between SMAD4 and coactivators were identified through reciprocal ChIP assays, expanding the understanding of the feedback regulation modes of TGF-beta family signaling pathways in ovarian GCs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Ning Zhang, Fang Guo, Yuanyuan Song
Summary: This study found that HOXC8 plays a crucial role in liver fibrosis by activating the TGF-b1 signaling pathway, promoting hepatic stellate cell activation and fibrosis. Inhibition of HOXC8 may serve as a promoting therapeutic strategy for liver fibrosis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Hee-Young Jeon, Majid Pornour, Hyunju Ryu, Sudeep Khadka, Rui Xu, Jihyun Jang, Deqiang Li, Hegang Chen, Arif Hussain, Ladan Fazli, Martin Gleave, Xuesen Dong, Furong Huang, Qianben Wang, Christopher Barbieri, Jianfei Qi
Summary: Overexpression of androgen receptor (AR) is the primary cause of castration-resistant prostate cancer, and this study reveals that SMAD3 plays a crucial role in upregulating AR expression by binding to intron 3 of the AR gene. Targeting SMAD3 binding sites can reduce AR levels and inhibit AR target gene expression. SMAD3 may also cooperate with or co-activate AR for AR target expression. These findings suggest that SMAD3 could be a potential target for inhibiting AR in prostate cancer.
NUCLEIC ACIDS RESEARCH
(2023)
Correction
Oncology
Roma Kaul, April L. Risinger, Susan L. Mooberry
Summary: An amendment has been published for this paper and can be accessed through a link at the top.
BRITISH JOURNAL OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Anyi Liu, Chengxin Yu, Cheng Qiu, Qi Wu, Changsheng Huang, Xun Li, Xiaowei She, Kairui Wan, Lang Liu, Mao Li, Zhihong Wang, Yaqi Chen, Fuqing Hu, Da Song, Kangdi Li, Chongchong Zhao, Haiteng Deng, Xuling Sun, Feng Xu, Senyan Lai, Xuelai Luo, Junbo Hu, Guihua Wang
Summary: Perturbations in TGF-beta signaling can be caused by mutations and posttranslational modifications of SMAD4, including R361 methylation mediated by PRMT5. This study demonstrates that the interaction between PRMT5 and SMAD4, as well as SMAD4 R361 methylation, play critical roles in TGF-beta signaling activation and metastasis. Blocking PRMT5-SMAD4 signaling could be a potential therapeutic strategy for SMAD4 wild-type CRC.
Article
Gastroenterology & Hepatology
Chenhao Zhou, Jialei Weng, Yuan Gao, Chunxiao Liu, Xiaoqiang Zhu, Qiang Zhou, Chia-Wei Li, Jialei Sun, Manar Atyah, Yong Yi, Qinghai Ye, Yi Shi, Qiongzhu Dong, Yingbin Liu, Mien-Chie Hung, Ning Ren
Summary: By analyzing immune-related genes, we identified a prognostic signature that is associated with the prognosis and immunotherapy response in hepatocellular carcinoma (HCC) patients. This signature accurately predicts overall survival rates and can assist in personalized clinical management.
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
(2022)
Article
Oncology
Xixi Zhao, Yongkun Wei, Yu-Yi Chu, Yintao Li, Jung-Mao Hsu, Zhou Jiang, Chunxiao Liu, Jennifer L. Hsu, Wei-Chao Chang, Riyao Yang, Li-Chuan Chan, Jingkun Qu, Shuqun Zhang, Haoqiang Ying, Dihua Yu, Mien-Chie Hung
Summary: This study reveals the role of CK2 in immunosuppression by phosphorylation and stabilization of PD-L1, and suggests CK2 inhibition as a potential immunotherapeutic approach for treating cancer.
Article
Biochemistry & Molecular Biology
Jong-Ho Cha, Li-Chuan Chan, Ying-Nai Wang, Yu-Yi Chu, Chie-Hong Wang, Heng-Huan Lee, Weiya Xia, Woei-Cherng Shyu, Shih-Ping Liu, Jun Yao, Chiung-Wen Chang, Fan-Ru Cheng, Jielin Liu, Seung-Oe Lim, Jennifer L. Hsu, Wen-Hao Yang, Gabriel N. Hortobagyi, Chunru Lin, Liuqing Yang, Dihua Yu, Long-Bin Jeng, Mien-Chie Hung
Summary: The expression of EphA10, a receptor tyrosine kinase, is associated with tumor progression and poor prognosis in several malignancies. This study demonstrates high expression levels of EphA10 in tumor regions and immune suppressive myeloid cells in the tumor microenvironment. The development of anti-EphA10 monoclonal antibodies and chimeric antigen receptor-T cell therapy targeting EphA10 shows potential as a promising strategy for patients with EphA10-positive tumors.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Riyao Yang, Linlin Sun, Ching-Fei Li, Yu-Han Wang, Weiya Xia, Boning Liu, Yu-Yi Chu, Laura Bover, Long Vien, Mien-Chie Hung
Summary: This study reports the development of two novel Gal-9-neutralizing antibodies that effectively protect human T cells from Gal-9-induced cell death and promote T cell-mediated killing of tumor cells. These findings demonstrate the potential of targeting Gal-9 for cancer immunotherapy.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Oncology
Simon Linder, Marlous Hoogstraat, Suzan Stelloo, Nils Eickhoff, Karianne Schuurman, Hilda de Barros, Maartje Alkemade, Elise M. Bekers, Tesa M. Severson, Joyce Sanders, Chia-Chi Flora Huang, Tunc Morova, Umut Berkay Altintas, Liesbeth Hoekman, Yongsoo Kim, Sylvan C. Baca, Martin Sjostrom, Anniek Zaalberg, Dorine C. Hintzen, Jeroen de Jong, Roelof J. C. Kluin, Iris de Rink, Claudia Giambartolomei, Ji-Heui Seo, Bogdan Pasaniuc, Maarten Altelaar, Rene H. Medema, Felix Y. Feng, Amina Zoubeidi, Matthew L. Freedman, Lodewyk F. A. Wessels, Lisa M. Butler, Nathan A. Lack, Henk van der Poel, Andries M. Bergman, Wilbert Zwart
Summary: In this study, the researchers performed integrative multi-omics analyses on prostate cancer patients before and after AR-targeted therapy. They found that AR inhibition drives tumors towards a neuroendocrine-like disease state, and identified ARNTL as a potential therapeutic target associated with clinical outcomes.
Article
Genetics & Heredity
Xabier Vergara, Ruben Schep, Rene H. Medema, Bas van Steensel
Summary: The traditional methods for studying DNA repair rely on fluorescence read-outs, while high throughput sequencing (HTS) has created new opportunities to understand the mechanisms behind double-strand break (DSB) repair.
Article
Biochemistry & Molecular Biology
Anoek Friskes, Lisa Koob, Lenno Krenning, Tesa M. Severson, Emma S. Koeleman, Xabier Vergara, Michael Schubert, Jeroen van den Berg, Bastiaan Evers, Anna G. Manjon, Stacey Joosten, Yongsoo Kim, Wilbert Zwart, Rene H. Medema
Summary: This study found that the location of double-strand breaks (DSBs) has little to no effect on their toxicity. The major determinants of toxicity for sgRNA are cutting efficiency and off-target effects.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Ziva Pogacar, Jackie L. Johnson, Lenno Krenning, Giulia De Conti, Fleur Jochems, Cor Lieftink, Arno Velds, Leyma Wardak, Kelvin Groot, Arnout Schepers, Liqin Wang, Ji-Ying Song, Marieke van de Ven, Olaf van Tellingen, Rene H. Medema, Roderick L. Beijersbergen, Rene Bernards, Rodrigo Leite de Oliveira
Summary: This study found that the use of the CDK2 inhibitor, indisulam, can enhance the induction of senescence in cancer cells by the CDK4/6 inhibitor, palbociclib, and sensitize the cells to senolytic therapy.
Correction
Oncology
Maud Kamal, Sonia Lameiras, Marc Deloger, Adeline Morel, Sophie Vacher, Charlotte Lecerf, Celia Dupain, Emmanuelle Jeannot, Elodie Girard, Sylvain Baulande, Coraline Dubot, Gemma Kenter, Ekaterina Jordanova, Els M. J. J. Berns, Guillaume Bataillon, Marina Popovic, Roman Rouzier, Wulfran Cacheux, Christophe Le Tourneau, Alain Nicolas, Nicolas Servant, Suzy Scholl, Ivan Bieche, RAIDs Consortium
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Claire Vennin, Chiara M. Cattaneo, Leontien Bosch, Serena Vegna, Xuhui Ma, Hugo G. J. Damstra, Moreno Martinovic, Efi Tsouri, Mila Ilic, Leyla Azarang, Jan R. T. van Weering, Emilia Pulver, Amber L. Zeeman, Tim Schelfhorst, Jeroen O. Lohuis, Anne C. Rios, Johanna F. Dekkers, Leila Akkari, Renee Menezes, Rene Medema, Serena R. Baglio, Anna Akhmanova, Sabine C. Linn, Simone Lemeer, Dirk M. Pegtel, Emile E. Voest, Jacco van Rheenen
Summary: Although treatment with taxanes may not always be effective, it carries the risk of side effects like peripheral neuropathy. A study found that taxanes can directly stimulate T cells to selectively kill cancer cells, independent of the T cell receptor. This mechanism involves the release of cytotoxic extracellular vesicles by T cells, inducing apoptosis specifically in tumor cells. These findings were utilized to develop a therapeutic approach using pre-treated T cells, avoiding systemic toxicity.
Article
Oncology
Lisa Koob, Anoek Friskes, Louise van Bergen, Femke M. Feringa, Bram van den Broek, Emma S. Koeleman, Ellis van Beek, Michael Schubert, Vincent A. Blomen, Thijn R. Brummelkamp, Lenno Krenning, Rene H. Medema
Summary: This study demonstrates that the meiotic recombination co-factor MND1 plays a role in the repair of DNA double-strand breaks (DSBs) in somatic cells. MND1 localizes to DSBs and stimulates DNA repair through homologous recombination (HR). Importantly, MND1 specifically functions in the repair response to two-ended DSBs induced by irradiation (IR) or chemotherapeutic drugs, and its activity is primarily observed in the G2 phase.
MOLECULAR ONCOLOGY
(2023)
Article
Cell Biology
Anna G. Manjon, Stefano Giustino Manzo, Stefan Prekovic, Leon Potgeter, Tom van Schaik, Ning Qing Liu, Koen Flach, Daniel Peric-Hupkes, Stacey Joosten, Hans Teunissen, Anoek Friskes, Mila Ilic, Dorine Hintzen, Vinicius H. Franceschini-Santos, Wilbert Zwart, Elzo de Wit, Bas van Steensel, Rene H. Medema
Summary: Acquired drug resistance is a major problem in cancer treatment. The study reveals that dissociation of the nuclear lamina can lead to derepression of the ABCB1 gene, resulting in drug resistance. This finding suggests that disruption of 3D genome topology plays an important role in tumor evolution and the acquisition of drug resistance.
Article
Oncology
Hsiao-Fan Chen, Po-Ren Hsueh, Yen-Yi Liu, Yeh Chen, Sui-Yuan Chang, Wei-Jan Wang, Chen-Shiou Wu, Ya-Min Tsai, Yu-Shu Liu, Wen-Chi Su, Yu-Chi Chou, Mien-Chie Hung
Summary: Disulfiram has shown potential as a therapy against COVID-19 by inhibiting viral replication and blocking viral entry into host cells. It has demonstrated activity against different variants of SARS-CoV-2 in molecular and cellular biology assays.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Oncology
Shih-Han Wang, Wen-Cheng Chou, Hsiang -Chi Huang, Te-An Lee, Tzu-Chun Hsiao, Ling -Hui Wang, Ke-Bin Huang, Chun-Tse Kuo, Chi -Hong Chao, Shing-Jyh Chang, Jung -Mao Hsu, Jialei Weng, Ning Ren, Fu -An Li, Yun-Ju Lai, Chenhao Zhou, Mien-Chie Hung, Chia -Wei Li
Summary: N-linked glycosylation of proteins is a post-translational modification that protects tumor antigens from immune attack. This study explores the role of N-glycosylation of SLAMF7 in breast cancer progression and highlights the potential strategy of using ADC to enhance immunotherapeutic agents through deglycosylation.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Oncology
Yi-Chuan Li, Hirohito Yamaguchi, Yen-Yi Liu, Kai-Cheng Hsu, Ting-Hsuan Sun, Pei-Chi Sun, Mien-Chie Hung
Summary: This article investigates the interaction between ribonuclease 1 (RNase1) and EphA4 and reveals their structure and role in cellular activation. The study suggests that electrostatic force plays a crucial role in the binding and activation of RNase1 and EphA4.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
