Article
Cell Biology
Anna-Christina Rambow, Insa Aschenbach, Sofie Hagelund, Doaa Tawfik, Jan-Paul Gundlach, Sebastian Weisse, Nicolai Maass, Anna Trauzold
Summary: Binding of TRAIL to its death domain-containing receptors TRAIL-R1 and TRAIL-R2 can induce cell death and/or pro-inflammatory signaling. The importance of TRAIL and TRAIL-R1/R2 in tumor immune surveillance and cancer biology has meanwhile been well documented. TRAIL also binds to TRAIL-R3 and TRAIL-R4, which have regulatory functions in apoptotic and non-apoptotic signaling pathways. Knockdown of TRAIL-R4 affects the activation of apoptotic and non-apoptotic pathways in cancer cells, showing opposing effects on cell death and clonogenic survival. TRAIL-R4 also regulates the expression of anti-apoptotic proteins and affects the activity of AKT, ERK, p38 and NF-kappa B. This study provides evidence for the important role of endogenous TRAIL-R4 in cancer cells and improves the understanding of the complex TRAIL/TRAIL-R system in humans.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Weiyan Yuan, Zhaokai Yao, Veeramohan Veerapandian, Xinyan Yang, Xiaoman Wang, Dingyao Chen, Linzi Ma, Chaohui Li, Yi Zheng, Fang Luo, Xiao-yang Zhao
Summary: The histone demethylase KDM2B is found to be highly expressed in male fetal germ cells (FGCs) and shares a similar expression pattern with hPGC marker genes in hPGCLCs. KDM2B plays an essential role in hPGCLC specification by suppressing somatic gene expression during primordial germ cell development.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Cell Biology
Sofie Hagelund, Anna Trauzold
Summary: TRAIL plays a crucial role in tumor immune surveillance and has the potential to kill cancer cells, but faces challenges in clinical trials. The external pH influences PDAC cells' response to TRAIL, with acidic pH adaptation showing the ability to enhance TRAIL sensitivity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Fang Yu, Jiangbo Wei, Xiaolong Cui, Chunjie Yu, Wei Ni, Jorg Bungert, Lizi Wu, Chuan He, Zhijian Qian
Summary: The RNA demethylase ALKBH5 serves as a key regulator in protecting cells from DNA damage and apoptosis during ROS-induced stress. ROS induces global mRNA N-6-methyladenosine levels by modulating ALKBH5 post-translational modifications, leading to the rapid induction of genes involved in DNA damage repair. Additionally, ROS activates the ERK/JNK/ALKBH5-PTMs/m(6)A axis in hematopoietic stem/progenitor cells in mice, indicating a physiological role of this pathway in maintaining genome stability.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Wenqi Xu, Jiahui Li, Chenxi He, Jing Wen, Honghui Ma, Bowen Rong, Jianbo Diao, Liyong Wang, Jiahua Wang, Feizhen Wu, Li Tan, Yujiang Geno Shi, Yang Shi, Hongjie Shen
Summary: METTL3 regulates mouse embryonic stem-cell heterochromatin, critical for silencing retroviral elements and mammalian development. Through m(6)A methylation, METTL3 modulates integrity of IAP heterochromatin.
Article
Chemistry, Medicinal
Xing-Jie Dai, Li-Juan Zhao, Long-Hua Yang, Ting Guo, Lei-Peng Xue, Hong-Mei Ren, Zhi-Li Yin, Xiao-Peng Xiong, Ying Zhou, Shi-Kun Ji, Hui-Min Liu, Hong-Min Liu, Ying Liu, Yi-Chao Zheng
Summary: In this study, the antipsychotic drug chlorpromazine was identified as an LSD1 inhibitor, and a series of chlorpromazine derivatives were synthesized. Among them, compound 3s showed the most potent inhibitory activity. Compound 3s inhibited LSD1 at the cellular level, downregulated PD-L1 expression in gastric cancer cells, and enhanced T-cell killing response. Animal studies confirmed that compound 3s can inhibit gastric cancer cell proliferation without significant toxicity in immunocompetent mice. These findings suggest that compound 3s may serve as a lead compound for further development to activate T-cell immunity in gastric cancer.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Nihal Karakas, Daniel Stuckey, Esther Revai-Lechtich, Khalid Shah
Summary: The study revealed that using IL13-PE or ENb-PE could upregulate TRAIL death receptors, suppress the expression of anti-apoptotic proteins, and sensitize highly resistant GBM cells to TRAIL-mediated apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2021)
Article
Chemistry, Multidisciplinary
Ashok Kumar Dhinakaran, Priya Dharmalingam, Swarna Ganesh, Krishnan Venkatakrishnan, Sunit Das, Bo Tan
Summary: This study highlights the potential of T cells as diagnostic markers for glioblastoma. By studying the phenotypic and immunological changes in T cells, two clinically validated biomarkers, GBMAT and GSCAT, were established. These biomarkers demonstrated high sensitivity and specificity in diagnosing GBM, and were further validated using a machine learning algorithm.
Article
Oncology
Amriti R. Lulla, Yan Zhou, Marie D. Ralff, Avital Lev, David T. Dicker, Wafik S. El-Deiry
Summary: TRAIL-based therapies are a promising approach for selectively killing cancer cells, but limited serum half-life hinders their clinical development. This study identifies a novel miRNA, miR-3132, which induces TRAIL and apoptosis in cancer cells via the interferon signaling pathway. This discovery provides new insights into the potential of miR-3132 as a therapeutic target for cancer treatment.
AMERICAN JOURNAL OF CANCER RESEARCH
(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
Cell Biology
Rosario Yerbes, Rocio Mora-Molina, F. Javier Fernandez-Farran, Laura Hiraldo, Abelardo Lopez-Rivas, Carmen Palacios
Summary: This study reveals a previously unknown cell death mechanism triggered in glutamine-addicted tumor cells in response to glutamine metabolism limitation. The mechanism is regulated by GCN2 activation induced by glutamine starvation and involves the activation of the extrinsic apoptotic pathway mediated by TRAIL-R2.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Korie A. Grayson, Jacob M. Hope, Wenjun Wang, Cynthia A. Reinhart-King, Michael R. King
Summary: Docetaxel and cabazitaxel alone do not significantly reduce cell viability in prostate cancer cells, indicating resistance to TRAIL and taxanes individually. However, the combination of taxanes and TRAIL synergistically enhances apoptosis, with taxanes sensitizing prostate cancer cells to TRAIL-induced apoptosis. Activation of JNK by ER stress upregulates death receptor expression and plays a role in sensitizing prostate cancer cells to TRAIL-induced apoptosis.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Cell Biology
Georgia Papadopoulou, Stavroula Petroulia, Eirini Karamichali, Alexios Dimitriadis, Dimitrios Marousis, Elisavet Ioannidou, Panagiota Papazafiri, John Koskinas, Pelagia Foka, Urania Georgopoulou
Summary: Hepatitis C virus (HCV) alters gene expression epigenetically to rearrange the cellular microenvironment in a beneficial way for its life cycle. Lysine-specific demethylase 1 (LSD1) is an epigenetic controller of critical cellular functions that are essential for HCV propagation. This study investigates the role of LSD1 in HCV infection and shows that LSD1 overexpression inhibits HCV replication, while inhibition of LSD1 increases viral replication. The study also suggests that LSD1 participates in an antiviral mechanism by activating IFITM3 via demethylation, leading to degradation of HCV virions.
Article
Oncology
Bo-Kyoung Jung, Yong Hee An, Sung Hoon Jang, Gyoungah Ryu, Saet-byel Jung, Seonhee Kim, Cuk-Seong Kim, Hyun Jang
Summary: This study found that Newcastle disease virus infection can enhance the expression of death receptors in colorectal cancer cells, increasing their sensitivity to the anticancer drug TRAIL. Additionally, the recombinant Newcastle disease virus containing the TRAIL gene showed better apoptotic efficacy than the traditional recombinant Newcastle disease virus therapy, and had a stronger killing effect on TRAIL-resistant cancer cells.
Article
Chemistry, Medicinal
Adriana G. Quiroz-Reyes, Paulina Delgado-Gonzalez, Jose F. Islas, Adolfo Soto-Dominguez, Carlos A. Gonzalez-Villarreal, Gerardo R. Padilla-Rivas, Elsa N. Garza-Trevino
Summary: This study evaluated the cytotoxic and proapoptotic activity of soluble TRAIL overexpressed by mesenchymal stem cells (MSC) in an oxaliplatin-resistant CRC cell line. The results demonstrated that oxaliplatin can enhance the apoptotic activity induced by soluble TRAIL.
Correction
Biotechnology & Applied Microbiology
Karl Petri, Weiting Zhang, Junyan Ma, Andrea Schmidts, Hyunho Lee, Joy E. Horng, Daniel Y. Kim, Ibrahim C. Kurt, Kendell Clement, Jonathan Y. Hsu, Luca Pinello, Marcela V. Maus, J. Keith Joung, Jing-Ruey Joanna Yeh
NATURE BIOTECHNOLOGY
(2022)
Article
Cell Biology
Yun Zhang, Joana Liu Donaher, Sunny Das, Xin Li, Ferenc Reinhardt, Jordan A. Krall, Arthur W. Lambert, Prathapan Thiru, Heather R. Keys, Mehreen Khan, Matan Hofree, Molly M. Wilson, Ozlem Yedier-Bayram, Nathan A. Lack, Tamer T. Onder, Tugba Bagci-Onder, Michael Tyler, Itay Tirosh, Aviv Regev, Jacqueline A. Lees, Robert A. Weinberg
Summary: Loss of PRC2 or KMT2D-COMPASS enables distinct epithelial-mesenchymal transition (EMT) trajectories in carcinoma cells, with differing effects on metastatic ability. These findings provide insight into how carcinoma cells control their entrance into and residence in different states, and which states are favorable for metastasis.
NATURE CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Jessica Whitburn, Srinivasa R. Rao, Emma Morris, Sho Tabata, Akiyoshi Hirayama, Tomoyoshi Soga, James R. Edwards, Zeynep Kaya, Charlotte Palmer, Freddie C. Hamdy, Claire M. Edwards
Summary: The energy requirements of prostate cancer cells change in the bone microenvironment, with the pentose phosphate pathway (PPP) and glucose-6-phosphate dehydrogenase (G6PD) playing a crucial role in bone metastasis. Inhibition of G6PD can reduce prostate cancer growth and migration, and increase chemosensitivity.
Article
Biochemistry & Molecular Biology
Nareg Pinarbasi-Degirmenci, Ilknur Sur-Erdem, Vuslat Akcay, Yasemin Bolukbasi, Ugur Selek, Ihsan Solaroglu, Tugba Bagci-Onder
Summary: By applying fractionated radiotherapy over a long time and selecting irradiation-survivor glioblastoma cells, clinically relevant irradiation-exposed models were generated. The cells exhibited slower growth, resistance to secondary irradiation, upregulation of DDR-related genes, and better DNA repair capacity. The utility of combining DDR inhibitors and irradiation was demonstrated for both naive and IR-Surv glioblastoma cells, as long as cells are refrained from hypoxic conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Ozlem Yedier-Bayram, Bengul Gokbayrak, Alisan Kayabolen, Ali Cenk Aksu, Ayse Derya Cavga, Ahmet Cingoz, Ezgi Yagmur Kala, Goktug Karabiyik, Rauf Gunsay, Beril Esin, Tunc Morova, Firat Uyulur, Hamzah Syed, Martin Philpott, Adam P. Cribbs, Sonia H. Y. Kung, Nathan A. Lack, Tamer T. Onder, Tugba Bagci-Onder
Summary: This study generated an epigenome-wide CRISPR-Cas9 knockout library (EPIKOL) to investigate the roles of epigenetic modifiers in cancer cells. Through eight screens in different cancer types, novel epigenetic modifiers regulating TNBC and prostate cancer cell fitness were identified. The results demonstrate that EPIKOL can be used to identify essential epigenetic modifiers and discover novel anti-cancer targets.
CELL DEATH & DISEASE
(2022)
Article
Chemistry, Multidisciplinary
Alisan Kayabolen, Ugur Akcan, Dogancan Ozturan, Hivda Ulbegi-Polat, Gizem Nur Sahin, Nareg Pinarbasi-Degirmenci, Canan Bayraktar, Gizem Soyler, Ehsan Sarayloo, Elif Nurtop, Berna Ozer, Gulen Guney-Esken, Tayfun Barlas, Ismail Selim Yildirim, Ozlem Dogan, Sercin Karahuseyinoglu, Nathan A. Lack, Mehmet Kaya, Cem Albayrak, Fusun Can, Ihsan Solaroglu, Tugba Bagci-Onder
Summary: Multimeric sACE2 demonstrates high neutralization efficiency and is a promising treatment approach against SARS-CoV-2 infections, surpassing the potency of monomeric sACE2 and effectively neutralizing variants of concern.
Article
Biology
Yingjun Liu, Assunta Senatore, Silvia Sorce, Mario Nuvolone, Jingjing Guo, Zeynep H. Gumus, Adriano Aguzzi
Summary: Cultured brain slices from mice upregulate senescence-associated genes and reproduce transcriptional characteristics of aged brains. Prions accelerate brain aging. This study establishes an innovative model system for studying brain aging.
COMMUNICATIONS BIOLOGY
(2022)
Correction
Biology
Yingjun Liu, Assunta Senatore, Silvia Sorce, Mario Nuvolone, Jingjing Guo, Zeynep H. Gumus, Adriano Aguzzi
COMMUNICATIONS BIOLOGY
(2022)
Review
Oncology
Qian Wang, Zeynep H. Gumus, Cristina Colarossi, Lorenzo Memeo, Xintong Wang, Chung Yin Kong, Paolo Boffetta
Summary: This article reviews research on the epidemiology, risk factors, genetic susceptibility, molecular pathology, and early detection of small cell lung cancer (SCLC). It summarizes the changing incidences of SCLC globally and in the United States, discusses the established risk factor of tobacco smoking, and highlights the importance of tobacco control. The review also explores genetic susceptibility, molecular pathology, and the limited utility of low-dose computed tomography screening in SCLC, as well as promising blood-based molecular biomarkers for early detection.
JOURNAL OF THORACIC ONCOLOGY
(2023)
Article
Oncology
Myvizhi Esai Selvan, Kenan Onel, Sacha Gnjatic, Robert J. Klein, Zeynep H. Gumus
Summary: Recent studies have shown that rare, deleterious variants (RDVs) in specific genes play a critical role in heritable cancer risk. By analyzing whole-exome sequencing data of 20,789 participants, we identified associations between cancer risk and RDVs in DNA repair, cancer predisposition, and somatic cancer drivers. Moreover, we found that personal RDV load in these gene-sets is associated with increased risk, earlier onset, increased M1 macrophages in tumor, and increased tumor mutational burden in specific cancers. These findings can be used to identify high-risk individuals and improve prognosis through increased surveillance, earlier screening, and targeted treatments.
NPJ PRECISION ONCOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Hande Suer, Suat Erus, Ekin E. Cesur, Omer Yavuz, Orhan Agcaoglu, Pinar Bulutay, Tamer T. Onder, Serhan Tanju, Sukru Dilege
Summary: Lung cancer is a highly metastatic form of cancer, and TNM staging is the gold standard for determining appropriate treatment. Traditional diagnostic methods may fail to detect micrometastasis, which can affect disease recurrence and survival. We found that a combination of gene expressions in lymph nodes can be used to identify micrometastasis and predict patients' recurrence and survival.
JOURNAL OF CARDIOTHORACIC SURGERY
(2023)
Article
Oncology
Ilknur Sur Erdem
Summary: This study investigated the role of ferroptosis in glioblastoma using a model of ionizing radiation survivor cells. The results showed that ferroptosis plays a critical role after radiation exposure in glioblastoma and suggested the potential use of ferroptosis-inducing agents in treating glioblastoma.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Safiye Cavdar, Busra Kose, Damlasu Altinoz, Gizem Soyler, Ahmet Cingoz, Ilke Ali Gurses, Mazhar Ozkan, Hizir Asliyuksek, Halit Cakir
Summary: This study demonstrates the presence of meningeal lymphatic vessels (mLVs) accompanying both dorsal and basal dural sinuses in the human brain using immunohistochemistry and Western Blotting techniques. The mLVs were found to have a larger size range in the dorsal dural sinuses compared to the basal dural sinuses, but a higher number in the basal dural sinuses.
JOURNAL OF CHEMICAL NEUROANATOMY
(2023)
Review
Biology
Walter Wolfsberger, Karishma Chhugani, Khrystyna Shchubelka, Alina Frolova, Yuriy Salyha, Oksana Zlenko, Mykhailo Arych, Dmytro Dziuba, Andrii Parkhomenko, Volodymyr Smolanka, Zeynep H. Guemues, Efe Sezgin, Alondra Diaz-Lameiro, Viktor R. Toth, Megi Maci, Eric Bortz, Fyodor Kondrashov, Patricia M. Morton, Pawel P. Labaj, Veronika Romero, Jakub Hlavka, Serghei Mangul, Taras K. Oleksyk
Summary: Conflicts and natural disasters not only cause destruction to lives, but also have a significant negative impact on the scientific advancements of the affected countries. These events result in infrastructure collapse, destruction of educational and research institutions, and hinder the progress of scientists. In our interconnected world, conflicts and disasters have far-reaching effects on the global community.
Correction
Biotechnology & Applied Microbiology
Karl Petri, Weiting Zhang, Junyan Ma, Andrea Schmidts, Hyunho Lee, Joy E. Horng, Daniel Y. Kim, Ibrahim C. Kurt, Kendell Clement, Jonathan Y. Hsu, Luca Pinello, Marcela V. Maus, J. Keith Joung, Jing-Ruey Joanna Yeh
NATURE BIOTECHNOLOGY
(2022)