Article
Multidisciplinary Sciences
Joshua Kim, Krista Chun, Jenna McGowan, Youjie Zhang, Piotr J. Czernik, Blair Mell, Bina Joe, Saurabh Chattopadhyay, Joseph Holoshitz, Ritu Chakravarti
Summary: Inflammatory arthritis (IA) is a common disease affecting millions worldwide. 14-3-3 zeta protein plays a role in immune suppression and extracellular remodeling, leading to previously unrecognized IA-suppressive function. Immunization with recombinant 14-3-3 zeta protein can suppress IL-1 beta levels and inhibit the progression of IA.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Cuixian Li, Shen Huang, Jin Peng, Tianguo Hong, Chun Zhou, Jie Tang
Summary: In this study, a new cellular protein, 14-3-3 zeta, was found to interact with the beta subunit of GABA(A)Rs and BIG1, and co-localize with them in hippocampal neurons. Overexpression of 14-3-3 zeta increased the surface expression of BIG1 and its binding with GABA(A)R. Depletion of 14-3-3 zeta or BIG1 significantly decreased GABA(A)R expression at the cell surface and inhibited GABA-gated influx of chloride ions.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Danielle M. Williams, David C. Thorn, Christopher M. Dobson, Sarah Meehan, Sophie E. Jackson, Joanna M. Woodcock, John A. Carver
Summary: 14-3-3 proteins are important in cellular signal transduction and act as molecular chaperones to maintain the protein structure of Aβ and α-syn by interacting preferentially with hydrophobic regions. The zeta isoform of 14-3-3 inhibits fibril formation of Aβ but has little effect on α-syn aggregation. These proteins play a role in the progression of Alzheimer's and Parkinson's diseases by interacting with amyloid-forming proteins.
Article
Pathology
Dan Wan, Yutao Zhang, Qin Yu, Feng Li, Junju Zhuo
Summary: The study revealed that the co-overexpression of 14-3-3 and HER2 in breast cancer could enhance the occurrence, development, and lymph node metastasis of the cancer, suggesting it may impact the treatment decisions and prognosis of breast cancer.
PATHOLOGY RESEARCH AND PRACTICE
(2021)
Article
Biochemistry & Molecular Biology
Sunayana Dagar, Kumari Pushpa, Diksha Pathak, Sarbani Samaddar, Anjana Saxena, Sourav Banerjee, Sivaram V. S. Mylavarapu
Summary: This study demonstrates a novel mRNA-guided mechanism of TNT formation through the maintenance of cellular 14-3-3 zeta mRNA levels by the RBP nucleolin.
Article
Oncology
Medine Zeynep Gungor, Merve Uysal, Serif Senturk
Summary: The TGF-beta signaling pathway has a dual and opposing role in hepatocellular carcinoma (HCC), acting as a tumor suppressor in the early stages and a promoter of tumor progression in the late stages. Therefore, targeting the TGF-beta signaling pathway is a promising therapeutic strategy for HCC.
Article
Fisheries
Rui Xue, Dinglong Yang, Yijing Han, Qinyou Deng, Xin Wang, Xiangquan Liu, Jianmin Zhao
Summary: The 14-3-3 zeta and 14-3-3 epsilon proteins play important roles in innate immunity against V. harveyi infection in mollusks, with their differential expression leading to different immune responses.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Phillip Zhu, Stanislau Stanisheuski, Rachel Franklin, Amber Vogel, Cat Hoang Vesely, Patrick Reardon, Nikolai N. Sluchanko, Joseph S. Beckman, P. Andrew Karplus, Ryan A. Mehl, Richard B. Cooley
Summary: 14-3-3 proteins dimerize and bind phosphorylated clients to regulate their function. By introducing stable mimics of phosphorylated amino acids, researchers can study 14-3-3 function effectively. In this study, the authors improved a previous genetic code expansion system to incorporate nonhydrolyzable phosphoserine into proteins. They successfully produced biologically relevant proteins with the modified amino acid and investigated the effects of phosphorylation on protein interactions and function.
ACS CENTRAL SCIENCE
(2023)
Article
Cell Biology
Yuan Huang, Shi Li, Qinfeng Liu, Zhijie Wang, Shunyao Li, Lei Liu, Weiwei Zhao, Kai Wang, Rui Zhang, Longfei Wang, Ming Wang, Declan William Ali, Marek Michalak, Xing-Zhen Chen, Cefan Zhou, Jingfeng Tang
Summary: This study reveals that lymphocyte-specific protein tyrosine kinase (LCK) directly interacts with transient receptor potential melastatin 8 (TRPM8) and enhances its phosphorylation at Y1022. LCK positively regulates TRPM8 channel function by increasing TRPM8 multimerization. Additionally, the interaction between TRPM8 and 14-3-3 zeta positively modulates channel multimerization. The phosphorylation of TRPM8 at Y1022 plays a crucial role in the proliferation, migration, and tumorigenesis of pancreatic cancer cells.
CELL DEATH & DISEASE
(2022)
Article
Multidisciplinary Sciences
Jacinth Rajendra, Atanu Ghorai, Shilpee Dutt
Summary: The study identified significant up-regulation of 14-3-3 zeta in residual resistant GBM cells, and knocking down this protein sensitized GBM cells to radiation therapy. Additionally, reduction of 14-3-3 zeta resulted in increased mitochondrial content in residual cells.
Article
Oncology
Mingda Zhao, Yibing Zhang, Longfei Li, Xiaobin Liu, Wenping Zhou, Chunhui Wang, Yufu Tang
Summary: Our study found that KHDRBS3 is highly expressed in human HCC tissues and predicts poor prognosis. Knockdown of KHDRBS3 inhibits tumor growth, reduces glycolysis, enhances sensitivity to doxorubicin, and induces apoptosis in HCC cells. On the contrary, overexpression of KHDRBS3 promotes malignant behavior. KHDRBS3 interacts with YWHAZ, and the promotion of proliferation and glycolysis and the inhibition of apoptosis caused by KHDRBS3 overexpression can be reversed by silencing 14-3-3ζ.
CANCER CELL INTERNATIONAL
(2023)
Article
Cell Biology
Zhaoxing Sun, Yichun Ning, Huan Wu, Shulan Guo, Xiaoyan Jiao, Ji Ji, Xiaoqiang Ding, Xiaofang Yu
Summary: This study found that 14-3-3 zeta plays a protective role in cisplatin-induced acute kidney injury by improving mitochondrial function and enhancing the balance between proliferation and apoptosis through facilitating the nuclear translocation of beta-catenin.
CELLULAR SIGNALLING
(2023)
Article
Biochemistry & Molecular Biology
Nikolai N. Sluchanko, Kristina Tugaeva, Ivan Gushchin, Alina Remeeva, Kirill Kovalev, Richard B. Cooley
Summary: Phosphorylation of the proapoptotic protein BAD regulates its association with 14-3-3 proteins, impacting cell fate. Unexpected phosphorylation at Ser74 instead of Ser75 on BAD peptide demonstrates plasticity of the amphipathic 14-3-3 groove in accommodating various peptides.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biology
Lei Song, Jingjing Luo, Hongou Wang, Dan Huang, Yunhao Tan, Yao Liu, Yingwu Wang, Kaiwen Yu, Yong Zhang, Xiaoyun Liu, Dan Li, Zhao-Qing Luo
Summary: In this study, a new bacterial effector Lem8 was found to modulate the function of host cytoskeleton and mediate the intracellular replication of Legionella pneumophila.
Article
Medicine, Research & Experimental
Kousuke Izumi, Shunhei Yamashina, Tsutomu Fujimura, Sumio Watanabe, Kenichi Ikejima
Summary: The study identified 14-3-3 zeta and importin alpha 4 as potential diagnostic biomarkers for liver diseases with autophagic disorders, as their levels were upregulated in the insoluble nuclear fraction following hepatic autophagy dysfunction and detectable in serum. The proteins translocated from cytoplasm to nucleus under autophagic dysfunction, and their expression was modulated by various factors such as autophagy inhibitor, EGF, insulin, or rapamycin.
Article
Gastroenterology & Hepatology
Christian David Schmid, Victor Olsavszky, Manuel Reinhart, Vanessa Weyer, Felix A. Trogisch, Carsten Sticht, Manuel Winkler, Sina W. Kurschner, Johannes Hoffmann, Roxana Ola, Theresa Staniczek, Joerg Heineke, Beate K. Straub, Jens Mittler, Kai Schledzewski, Peter ten Dijke, Karsten Richter, Steven Dooley, Cyrill Geraud, Sergij Goerdt, Philipp-Sebastian Koch
Summary: This study established an HHT mouse model with liver vascular malformations and investigated the role of ALK1 signaling in liver vessel formation and metabolic function. The results showed that hepatic endothelial ALK1 signaling protects from development of vascular malformations and preserves organ-specific endothelial differentiation and angiocrine signaling.
Article
Biochemistry & Molecular Biology
Jing Zhang, Maarten van Dinther, Midory Thorikay, Babak Mousavi Gourabi, Boudewijn P. T. Kruithof, Peter ten Dijke
Summary: Ubiquitin-specific protease (USP)19 is a deubiquitinating enzyme that regulates protein stability and function, with its alternative splicing resulting in two major variants localized to the endoplasmic reticulum and cytoplasm. USP19-CY promotes TGF-beta signaling by interacting with the TGF-beta type I receptor and preventing its degradation at the plasma membrane, while USP19-ER sequesters the receptor in the ER and inhibits TGF-beta/SMAD signaling. Increased USP19-CY expression is associated with poor prognosis and higher levels in breast cancer tissues, where it enhances epithelial-mesenchymal transition and cell migration. Modulating USP19 splicing or deubiquitinating activity may hold therapeutic potential for breast cancer.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jing Zhang, Gerard van Der Zon, Jin Ma, Hailiang Mei, Birol Cabukusta, Cedrick C. Agaser, Katarina Madunic, Manfred Wuhrer, Tao Zhang, Peter ten Dijke
Summary: Epithelial-mesenchymal transition (EMT) is important in cancer cell metastasis. The abundance of glycosphingolipids (GSLs), specifically ganglioside subtypes, decreases during TGF-beta-induced EMT. Inhibition of UDP-glucose ceramide glucosyltransferase (UGCG), the enzyme responsible for GSL biosynthesis, promotes TGF-beta signaling and EMT. ST3GAL5-synthesized a-series gangliosides inhibit TGF-beta signaling and EMT in lung cancer cells.
Letter
Oncology
Yang Hao, Sen Ma, Zili Gu, Alireza Haghparast, Timo Schomann, Zhenfeng Yu, Yuanyuan He, Xiaoxv Dong, Luis J. Cruz, Peter ten Dijke
CANCER COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Chuannan Fan, Qian Wang, Thomas B. Kuipers, Davy Cats, Prasanna Vasudevan Iyengar, Sophie C. Hagenaars, Wilma E. Mesker, Peter Devilee, Rob A. E. M. Tollenaar, Hailiang Mei, Peter ten Dijke
Summary: In this study, the researchers found that the long noncoding RNA LITATS1 functions as an epithelial gatekeeper and inhibits epithelial-mesenchymal transition in breast and non-small cell lung cancer cells. They also discovered that LITATS1 enhances the degradation of the TGF-beta type I receptor, leading to the attenuation of TGF-beta/SMAD signaling and EMT.
Article
Oncology
Sijia Liu, Maarten van Dinther, Sophie C. Hagenaars, Yuanzhuo Gu, Thomas B. Kuipers, Hailiang Mei, Maria Catalina Gomez-Puerto, Wilma E. Mesker, Peter ten Dijke
Summary: Triple-negative breast cancer (TNBC) is a challenging subtype due to its aggressive nature and low response to current therapies. Understanding TNBC metastasis may lead to better diagnosis and treatment options. In this study, OPTN was found to play a surprising role in inhibiting TNBC metastasis by suppressing the TGF beta signaling pathway. These findings suggest that OPTN may be a potential target for suppressing TNBC metastasis.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Dieuwke L. Marvin, Jelmer Dijkstra, Rabia M. Zulfiqar, Michiel Vermeulen, Peter ten Dijke, Laila Ritsma
Summary: Melanoma patients with liver metastasis have a poor prognosis. The cytokine Transforming Growth Factor beta (TGF-beta) plays a role in melanoma cells and acts on cells in the liver. We hypothesized that this cytokine influences the metastatic outgrowth of melanoma in liver. To investigate this, we generated a model to turn on and off TGF-beta signaling in the B16F10 melanoma cells, and found that TGF-beta activation repressed cell growth and migration in vitro, while it increased outgrowth in liver in vivo.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Zili Gu, Yang Hao, Timo Schomann, Ferry Ossendorp, Peter ten Dijke, Luis J. Cruz
Summary: The cGAS-STING pathway acts as a bridge between innate and adaptive immunity, making it a promising approach for anti-cancer immunotherapy. Chemotherapy-induced DNA damage can directly induce dendritic cell maturation and recruitment, which synergizes with STING activation to enhance anti-tumor effects. In this study, liposomes encapsulating oxaliplatin were developed and combined with a STING agonist to treat colorectal cancer, resulting in complete remission of tumors. Mechanistic studies showed that this treatment resulted in the recruitment of infiltrating CD8 and CD4 T cells, reduction of suppressive Treg cells, and a shift in the phenotype of tumor-associated suppressive macrophages, leading to an immune-stimulating environment.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Biochemistry & Molecular Biology
Chuannan Fan, Roman Gonzalez-Prieto, Thomas B. Kuipers, Alfred C. O. Vertegaal, Peter A. van Veelen, Hailiang Mei, Peter ten Dijke
Summary: We identified an unannotated nuclear long noncoding RNA (lncRNA), LETS1, which is not only increased but also perpetuated by TGF-beta signaling. Loss of LETS1 attenuated TGF-beta-induced EMT and migration in breast and lung cancer cells in vitro and extravasation of the cells in a zebrafish xenograft model. LETS1 potentiates TGF-beta-SMAD signaling by stabilizing cell surface T beta RI, thereby forming a positive feedback loop.
Article
Oncology
Edward P. Carter, Kubra K. Yoneten, Nuria Gavara, Eleanor J. Tyler, Valentine Gauthier, Elizabeth R. Murray, Peter ten Dijke, Angus J. Cameron, Oliver Pearce, Richard P. Grose
Summary: The crosstalk between cancer and stellate cells is crucial in the progression of pancreatic cancer. Through transcriptomic analysis, the study identified the specific expression of enzymes ADAMTS2 and ADAMTS14 in stellate cells, which regulate myofibroblast differentiation by modulating the availability of transforming growth factor beta.
JOURNAL OF PATHOLOGY
(2023)
Article
Multidisciplinary Sciences
Maarten van Dinther, Kyle T. Cunningham, Shashi Prakash Singh, Madeleine P. J. White, Tiffany Campion, Claire Ciancia, Peter A. van Veelen, Arnoud H. de Ru, Roman Gonzalez-Prieto, Ananya Mukundan, Chang- Hyeock Byeon, Sophia R. Staggers, Cynthia S. Hinck, Andrew P. Hinck, Peter ten Dijke, Rick M. Maizels
Summary: This study investigates how the murine intestinal helminth, Heligmosomoides polygyrus, evades the host immune system through the release of an immunosuppressive protein called TGM1. The researchers found that TGM1 binds to the cell surface protein CD44, increasing the potency and specificity of TGF-beta signaling in mammalian cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Yuanzhuo Gu, Zhengkui Zhang, Marcel G. M. Camps, Ferry Ossendorp, Ruud H. Wijdeven, Peter ten Dijke
Summary: The genetic circuits allowing cancer cells to evade immune killing through epithelial mesenchymal plasticity are poorly understood. This study found that mesenchymal-like pancreatic cancer cells were more resistant to cytotoxic T lymphocyte (CTL)-mediated killing than epithelial-like cells. Genome-wide CRISPR screens were used to identify the molecular mechanisms underlying this difference. It was discovered that Mes-specific regulators such as Egfr and Mfge8 facilitate immune escape from CD8(+) T cells by inhibiting their proliferation and the production of immune signaling molecules.
Review
Medicine, Research & Experimental
Yang Hao, Zhonghao Ji, Hengzong Zhou, Dongrun Wu, Zili Gu, Dongxu Wang, Peter ten Dijke
Summary: Immune checkpoint inhibitors (ICIs) have shown remarkable success in cancer treatment. However, in cancer patients without sufficient antitumor immunity, blocking the negative signals elicited by immune checkpoints is ineffective. Stimulating immune activation-related pathways and utilizing nanotechnology for targeted delivery show promising potential for enhancing cancer immunotherapy. This review discusses the latest developments in lipid-based nanoparticles (lipid-NPs) for cancer immuno-oncology therapy, focusing on their characteristics, advantages, and potential to enhance STING agonist therapy.
Article
Oncology
Christianne Groeneveldt, Jurriaan Q. Ginkel, Priscilla Kinderman, Marjolein Sluijter, Lisa Griffioen, Camilla Labrie, Diana J. M. van den Wollenberg, Rob C. Hoeben, Sjoerd H. van der Burg, Peter ten Dijke, Lukas J. A. C. Hawinkels, Thorbald van Hall, Nadine van Montfoort
Summary: The absence of T cells in the tumor microenvironment is a barrier to cancer immunotherapy efficacy. Oncolytic viruses, such as reovirus type 3 Dearing (Reo), can recruit CD8(+) T cells to the tumor and enhance immunotherapeutic strategies. However, TGF-beta signaling might hinder the effectiveness of Reo&CD3-bsAb therapy due to its immunoinhibitory characteristics.
CANCER RESEARCH COMMUNICATIONS
(2023)
Review
Immunology
Yuanzhuo Gu, Zhengkui Zhang, Peter ten Dijke
Summary: Immune checkpoint blockade (ICB) therapy is a powerful option for cancer treatment, but many patients are resistant to this treatment. Tumor epithelial-to-mesenchymal plasticity (EMP) plays a critical role in immune escape and ICB resistance in cancer. This review summarizes the role of tumor EMP in ICB resistance and discusses strategies to modulate it for better treatment outcomes.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
