Article
Biology
Robert Malory Alarcon Flores, Simone Queiroz Pantaleao, Sheila Cruz Araujo, Humberto Miguel Garay Malpartida, Kathia Maria Honorio
Summary: FAM3 is a superfamily of cytokines that have a crucial role in cancer progression, particularly FAM3C which induces epithelial-mesenchymal transition (EMT). Despite extensive research on the role of FAM3C in cancer and other diseases, little is known about its cellular receptors and possible inhibitors. In this study, structural analyses of factors related to FAM3C/ILEI dimerization were performed, and four potential inhibitor candidates were identified for future biological tests targeting cancer treatment.
COMPUTATIONAL BIOLOGY AND CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Ulrike Schmidt, Betuel Uluca, Iva Vokic, Barizah Malik, Thomas Kolbe, Caroline Lassnig, Martin Holcmann, Veronica Moreno-Viedma, Bernhard Robl, Carina Muehlberger, Dagmar Gotthardt, Maria Sibilia, Thomas Ruelicke, Mathias Mueller, Agnes Csiszar
Summary: FAM3C/ILEI is an important factor in epithelial-to-mesenchymal transition (EMT) induction, tumor progression, and metastasis. In this study, the researchers generated a new Tet-ON inducible Fam3c/ILEI transgenic mouse strain, providing a versatile tool to model the effect of elevated ILEI expression in various tissue entities and disease conditions, including cancer.
Article
Biochemistry & Molecular Biology
Naoki Watanabe, Masaki Nakano, Yachiyo Mitsuishi, Norikazu Hara, Tatsuo Mano, Atsushi Iwata, Shigeo Murayama, Toshiharu Suzuki, Takeshi Ikeuchi, Masaki Nishimura
Summary: The study revealed that the downregulation of FAM3C in the AD brain may be a risk factor for A beta accumulation and eventually AD development. Transcriptional mechanisms involving SP1, EBF1, SMAD1, and KLF6 were identified as factors influencing the expression of FAM3C, with reduced nuclear levels of SP1 and EBF1 in AD brains contributing to the observed transcriptional downregulation.
HUMAN MOLECULAR GENETICS
(2022)
Article
Oncology
Ulrike Schmidt, Gerwin Heller, Gerald Timelthaler, Petra Heffeter, Zsolt Somodi, Norbert Schweifer, Maria Sibilia, Walter Berger, Agnes Csiszar
Summary: The study found that FAMC3 is strictly associated with MET amplification in multiple human cancers and cancer cell lines. Increased copy numbers of FAM3C and MET were tightly linked and correlated with increased gene expression and poor survival in human lung cancer, as well as extramural invasion in colorectal carcinoma.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Medicine, Research & Experimental
Barizah Malik, Iva Vokic, Thomas Mohr, Marle Poppelaars, Martin Holcmann, Philipp Novoszel, Gerald Timelthaler, Thomas Lendl, Dana Krauss, Ulrich Elling, Michael Mildner, Josef M. Penninger, Peter Petzelbauer, Maria Sibilia, Agnes Csiszar
Summary: This study reveals that ILEI protein is highly expressed in psoriatic lesions and plays a key role in the development of psoriasis through the activation of Erk, Akt, and STAT3 signaling pathways. It also identifies urokinase as a potential therapeutic target for psoriasis treatment. Inhibition of urokinase significantly improves psoriasiform symptoms in a mouse model with keratinocyte-specific ILEI overexpression.
EMBO MOLECULAR MEDICINE
(2023)
Review
Medicine, Research & Experimental
Yuanyuan Zhu, Zhangya Pu, Guoqiang Wang, Yubin Li, Yinmiao Wang, Ning Li, Fang Peng
Summary: FAM3C, a member of the FAM3 family, has been reported to be overexpressed in various types of cancer and associated with tumor formation, invasion, metastasis, and poor survival. It is also known to regulate proteins like Ras, STAT3, TGF-beta, and LIFR, which are linked to cancer. This suggests that FAM3C could be a novel biomarker and potential therapeutic target for cancer treatment.
BIOMARKERS IN MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Yaohui Wang, Xiang Li, Tiancheng Zhang, Fangyuan Li, Yuke Shen, Yani He, Qiang You, Yifan Zhang, Jing Zhai, Xuequan Yao, Lizong Shen
Summary: In gastric cancer, tumor-associated neutrophils (TANs) promote lymph node metastasis (LNM) through enhancing tumor cell invasiveness and epithelial-to-mesenchymal transition (EMT). The crosstalk between neutrophils and tumor cells is mediated by various signaling pathways including TGF beta 1, FAM3C, and JNK-ZEB1/Snail, and involves interaction of integrins alpha 6 beta 1 and alpha 6 beta 4 with CD151. Studies using tumor-bearing mice confirm the importance of neutrophils in gastric cancer tumorigenesis and invasiveness. Understanding the functional roles of TANs in promoting tumor invasion provides potential targets for developing strategies to prevent or treat LNM in gastric cancer.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Medicine, Research & Experimental
Feng Bai, Li-Han Zhang, Xiong Liu, Chuying Wang, Chenglong Zheng, Jianping Sun, Min Li, Wei-Guo Zhu, Xin-Hai Pei
Summary: The study reveals a positive correlation between BRCA1 and GATA3 expression in human breast cancers. Depletion of BRCA1 stimulates methylation of GATA3 promoter, repressing GATA3 transcription. Additionally, GATA3 deficiency induces poorly-differentiated mammary tumors with activated EMT and increased metastatic potential.
Review
Cell Biology
Rongyu Zhang, Jinghong Chen, Saiyang Wang, Wenlong Zhang, Quan Zheng, Rong Cai
Summary: Ferroptosis is an iron-dependent form of regulated cell death associated with processes including iron overload, lipid peroxidation, and dysfunction of cellular antioxidant systems. Recent studies have shown its close relationship with cancer progression, including EMT, cancer angiogenesis, invasion, and metastasis. The signaling pathways activated during ferroptosis and cancer metastasis interweave, and ferroptosis may serve as a potential predictor of cancer grades and prognoses.
Review
Biochemistry & Molecular Biology
Misung Park, Dohee Kim, Sunghyub Ko, Ayoung Kim, Kyumin Mo, Hyunho Yoon
Summary: Breast cancer is the most common malignancy in women worldwide, and metastasis is the leading cause of high mortality. Currently, breast cancer is often discovered or diagnosed after metastasis has occurred, resulting in poor prognosis. Understanding the mechanisms and nature of breast cancer metastasis can facilitate the development of targeted therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
David P. Cook, Barbara C. Vanderhyden
Summary: Epithelial-mesenchymal plasticity (EMP) is closely related to tumor progression, therapy resistance and immune cell evasion. By analyzing single-cell RNA sequencing data, we found diverse EMP expression patterns within tumors, which are regulated by various mechanisms initiated from the tumor microenvironment. Inferring regulatory features can provide effective therapeutic strategies to restrict EMP.
Article
Biochemistry & Molecular Biology
Huiling Zhou, Qing Guan, Xuyang Hou, Lijun Liu, Li Zhou, Wei Li, Haidan Liu
Summary: Our study reveals that Rictor is highly expressed in NSCLC and regulated transcriptionally, with its interaction with KLF4 affecting the migration and invasion ability of NSCLC cells.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Junfeng Ke, Wenzhao Han, Fanwei Meng, Feng Guo, Yuhong Wang, Liping Wang
Summary: Studies have shown that CTI-2 inhibits the activation of the MAPK signaling pathway, reduces the expression of E-cadherin, N-cadherin, and vimentin, thus preventing the metastasis of breast cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Medicine, Research & Experimental
Lin Zhou, Zhe Zhang, Yizhou Tian, Zefei Li, Zhongliang Liu, Sibo Zhu
Summary: Platelets play a crucial role in cancer metastasis by activating and modulating cancer cells, promoting their progression and protecting them from immune surveillance and cell death.
EUROPEAN JOURNAL OF MEDICAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Maria do Carmo Greier, Annette Runge, Jozsef Dudas, Viktoria Pider, Ira-Ida Skvortsova, Dragana Savic, Herbert Riechelmann
Summary: Mitochondrial dysfunction can induce epithelial mesenchymal transition in head and neck cancer cell lines, thereby promoting cancer aggressiveness and metastasis. However, this phenomenon is observed only in one of the cell lines.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Betul Uluca, Cemre Lektemur Esen, Sinem Saritas Erdogan, Asli Kumbasar
Summary: This study reveals the role of Nuclear Factor One (NFI) family of transcription factors in neuroblastoma. NFIB is crucial for the survival and proliferation of SHSY5Y neuroblastoma cells, and regulates the expression of tumor suppressor CDON. Moreover, NFIB knock-down also leads to upregulation of other molecules such as p21.
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2022)
Article
Biochemical Research Methods
Stefan Rudloff, Andrea Bileck, Lukas Janker, Nicola Wanner, Nastassia Liaukouskaya, Carsten Lundby, Tobias B. Huber, Christopher Gerner, Uyen Huynh-Do
Summary: This research focuses on the response of fetal kidney to chronic hypoxia and explores the key events that lead to accelerated aging in chronic hypoxic human diseases. The study reveals a dichotomous response in fetal kidneys, with both cellular adaptations for survival and processes inducing a senescence-like phenotype. Additionally, the expression of antiaging proteins is reduced under chronic hypoxia. These findings provide a solid foundation for the hypothesis of fetal programming of adult diseases and offer potential biomarkers for detecting and targeting accelerated aging in chronic hypoxic human diseases.
MOLECULAR & CELLULAR PROTEOMICS
(2022)
Article
Chemistry, Multidisciplinary
Samuel M. Meier-Menches, Benjamin Neuditschko, Lukas Janker, Marlene C. Gerner, Klaus G. Schmetterer, Albrecht Reichle, Christopher Gerner
Summary: The combination treatment of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) for acute promyelocytic leukemia (APL) provides a compelling alternative to traditional chemotherapy, but lacks an in vitro model for testing novel combination treatments. Through proteome profiling, the effects of differentiation and metal-specific treatments were characterized in various acute myeloid leukemia (AML) cell lines, revealing significant impacts on the proteome and distinct responses to ATO. The study also proposed a novel metal-based compound, plecstatin-1, as a potential alternative to ATO based on its effects on different cell lines.
FRONTIERS IN CHEMISTRY
(2022)
Article
Medicine, General & Internal
Julia Brunmair, Andrea Bileck, Doreen Schmidl, Gerhard Hagn, Samuel M. Meier-Menches, Nikolaus Hommer, Andreas Schlatter, Christopher Gerner, Gerhard Garhoefer
Summary: This study investigated the metabolic composition of human tears compared to finger sweat in order to identify biofluid-specific marker molecules. Tear fluid analysis can provide insights into eye pathologies and also predict and monitor the progression and treatment of systemic disorders such as type 2 diabetes mellitus. Tear fluid was found to be a rich source for metabolic phenotyping and several molecules previously identified in sweat were significantly enriched in tears. Tear fluid analysis has the potential to support disease development prediction and individualized treatments.
Article
Biochemical Research Methods
Diana Santacruz, Francis O. Enane, Katrin Fundel-Clemens, Martin Giner, Gernot Wolf, Svenja Onstein, Christoph Klimek, Zachary Smith, Bhagya Wijayawardena, Coralie Viollet
Summary: RNA-seq has become a reliable method for unbiased assessment of gene expression, and integrating it with other omics datasets enhances our understanding of cell-specific regulatory patterns. However, the time-consuming library preparation process has been a bottleneck. To address this issue, an automated workflow was designed to increase efficiency.
Article
Chemistry, Multidisciplinary
Valentin Fuchs, Klaudia Cseh, Michaela Hejl, Petra Vician, Benjamin Neuditschko, Samuel M. Meier-Menches, Lukas Janker, Andrea Bileck, Natalie Gajic, Julia Kronberger, Martin Schaier, Sophie Neumayer, Gunda Koellensperger, Christopher Gerner, Walter Berger, Michael A. Jakupec, Michael S. Malarek, Bernhard K. Keppler
Summary: A series of highly lipophilic Cp-substituted molybdenocenes with different bioactive chelating ligands were synthesized and characterized. They showed significantly increased cytotoxic potency compared to non-Cp-substituted counterparts. In vivo experiments demonstrated tumor growth inhibition for the most active complex containing the thioflavone ligand, along with significant regulation of tubulin-associated and mitochondrial inner membrane proteins.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Review
Biochemistry & Molecular Biology
Yasmin Borutzki, Lukas Skos, Christopher Gerner, Samuel M. Meier-Menches
Summary: In recent years, metal-based candidate drugs have shown promise as modulators of cytoskeletal and cytoskeleton-associated proteins. Actin, vimentin, and plectin have been identified as targets of ruthenium(II) and platinum(II)-based modulators. However, there is limited structural information available on molecular interactions. This article compiles scattered reports on metal-based candidate molecules influencing the cytoskeleton and its associated proteins, exploring their potential in cancer-related processes.
Article
Cell Biology
Katrin Colleselli, Marie Ebeyer-Masotta, Benjamin Neuditschko, Anna Stierschneider, Christopher Pollhammer, Mia Potocnjak, Harald Hundsberger, Franz Herzog, Christoph Wiesner
Summary: The interaction between monocytes and endothelial cells plays a key role in inflammation, including chemoattraction, adhesion, and transendothelial migration. Toll-like receptor 2 (TLR2) is critical for sensing pathogens and initiating an immune response. In this study, we found that TLR2 promotes monocyte adhesion to endothelial cells, disrupts the endothelial barrier, and affects actin polymerization. Our findings also revealed the association of TLR2 with specific integrins and identified novel proteins affected by TLR2.
Article
Cell Biology
Huriye Ercan, Ulrike Resch, Felicia Hsu, Goran Mitulovic, Andrea Bileck, Christopher Gerner, Jae-Won Yang, Margarethe Geiger, Ingrid Miller, Maria Zellner
Summary: Proteomics is an essential analytical technique for studying biological systems using different proteins. The study compared the qualitative and quantitative performance of two commonly used proteomics techniques, label-free shotgun and 2D-DIGE, using six technical and three biological replicates of the human prostate carcinoma cell line DU145. The results showed that label-free shotgun quickly provides an annotated proteome but with reduced robustness compared to 2D-DIGE, which offers qualitative and quantitative information on proteoforms and post-translational modifications. However, the 2D-DIGE technique requires more time and manual work. Ultimately, this work highlights the different outputs and applications of these two techniques for biological research.
Article
Cell Biology
Anna Stierschneider, Benjamin Neuditschko, Katrin Colleselli, Harald Hundsberger, Franz Herzog, Christoph Wiesner
Summary: Optogenetic cell lines based on light-oxygen-voltage-sensing (LOV) domains (opto-TLR4-LOV LECs and opto-TLR4-LOV HUVECs) allow fast, precise, and reversible activation of TLR4 signaling pathways, providing a better simulation of inflammatory responses than LPS. Light-induced TLR4 activation can promote the expression of inflammatory proteins and significantly impact cell function and cell migration. This technology enables specific studies of TLR4.
Article
Biochemistry & Molecular Biology
Franziska Ferk, Miroslav Misik, Benjamin Ernst, Gerhard Prager, Christoph Bichler, Doris Mejri, Christopher Gerner, Andrea Bileck, Michael Kundi, Sabine Langie, Klaus Holzmann, Siegfried Knasmueller
Summary: Obesity causes genetic instability, which is a key factor in the development of cancer and aging. This study investigated the effects of bariatric surgery on DNA repair, oxidative DNA damage, telomere lengths, antioxidant enzymes, and inflammation-related proteins. The results showed that after 6 months, bariatric surgery led to weight reduction, decreased DNA damage and oxidized DNA bases, lower levels of malondealdehyde, increased DNA repair and telomere lengths, and downregulation of inflammation-related proteins. These findings suggest that bariatric surgery can reduce DNA damage and inflammation, resulting in long-term health benefits.
Article
Cell Biology
Alexander Ries, Astrid Slany, Christine Pirker, Johanna C. C. Mader, Doris Mejri, Thomas Mohr, Karin Schelch, Daniela Flehberger, Nadine Maach, Muhammad Hashim, Mir Alireza Hoda, Balazs Dome, Georg Krupitza, Walter Berger, Christopher Gerner, Klaus Holzmann, Michael Grusch
Summary: In this study, novel hTERT-transduced mesothelial cell and Meso-CAF models were generated and characterized, and their impact on PM cell growth was investigated.
Meeting Abstract
Medicine, General & Internal
T. M. Hofbauer, K. Distelmaier, A. Bileck, A. S. Ondracek, S. Kuehn, V Seidl, A. Aszlan, B. Neuditschko, D. Pils, C. Gerner, I. M. Lang
WIENER KLINISCHE WOCHENSCHRIFT
(2022)
Article
Medicine, Research & Experimental
Kathrin Liszt, Qiaoling Wang, Mona Farhadipour, Anneleen Segers, Theo Thijs, Linda Nys, Ellen Deleus, Bart van der Schueren, Christopher Gerner, Benjamin Neuditschko, Laurens J. Ceulemans, Matthias Lannoo, Jan Tack, Inge Depoortere
Summary: Taste 2 receptors (TAS2Rs) in the human gut play a key role in detecting potentially toxic food. The study found that human jejunal crypts, especially in individuals with obesity, respond to bitter substances by releasing antimicrobial peptides and regulating other immune factors that affect the growth of E. coli. The study also identified the role of TAS2R43 in the effects of aloin on E. coli growth and mucus glycoprotein release. Additionally, the study revealed the potential of TAS2Rs as a target for treating diseases related to the immune system and body weight control.
JOURNAL OF CLINICAL INVESTIGATION
(2022)