Article
Cell Biology
Jagyeong Oh, Davide Pradella, Changwei Shao, Hairi Li, Namjeong Choi, Jiyeon Ha, Sonia Ruggiero, Xiang-Dong Fu, Xuexiu Zheng, Claudia Ghigna, Haihong Shen
Summary: Aberrant alternative splicing in breast cancer is linked to disease progression, metastasis, and patient survival. High-metastatic breast cancer cells exhibit different AS choices in genes related to cancer progression compared to low-metastatic cells. Analysis reveals novel AS features in metastatic breast tumors.
Article
Multidisciplinary Sciences
Xiaolin Wang, Jingxin Li, Xing Bian, Cheng Wu, Jinghan Hua, Shuhui Chang, Tianyi Yu, Hong Li, Yongxiang Li, Shanshan Hu, Ge Shan, Wenchu Lin
Summary: The study identified circURI7 as a circRNA with significantly higher expression in gastric cancer, which inhibits cell migration and invasion by modulating alternative splicing of genes involved in the process of cell migration, thus suppressing GC metastasis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Ling Deng, Li Liao, Yin-Ling Zhang, Shu-Yuan Hu, Shao-Ying Yang, Xiao-Yan Ma, Min-Ying Huang, Fang-Lin Zhang, Da-Qiang Li
Summary: We found that U2SURP protein expression was significantly upregulated in TNBC tissues and associated with poor prognosis. U2SURP promoted alternative splicing of SAT1 pre-mRNA, resulting in increased stability of SAT1 mRNA and subsequent protein expression, thereby promoting the oncogenic properties of TNBC cells.
Article
Oncology
Yao-Jie Pan, Fu-Chun Huo, Meng-Jie Kang, Bo-Wen Liu, Meng-Di Wu, Dong-Sheng Pei
Summary: SRSF11 is found to be overexpressed in colorectal cancer (CRC) and associated with poor prognosis. It plays a pro-metastatic role in both in vitro and in vivo settings. The study highlights the relationship between SRSF11-regulated splicing and CRC metastasis, suggesting a potential therapeutic target and prognostic biomarker in CRC.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
Jagyeong Oh, Davide Pradella, Yoonseong Kim, Changwei Shao, Hairi Li, Namjeong Choi, Jiyeon Ha, Anna Di Matteo, Xiang-Dong Fu, Xuexiu Zheng, Claudia Ghigna, Haihong Shen
Summary: Aberrant alternative splicing (AS) regulation is crucial in breast cancer development, progress, and resistance to therapy. Our study identified dysregulated AS events in breast cancer cells, shedding light on the molecular mechanisms underlying malignant transformation. Analysis revealed that aberrantly regulated AS events in cancer tissues encode for regions with high flexibility and potential for modifications, impacting breast cancer biology.
Review
Oncology
Jose J. G. Marin, Maria Reviejo, Meraris Soto, Elisa Lozano, Maitane Asensio, Sara Ortiz-Rivero, Carmen Berasain, Matias A. Avila, Elisa Herraez
Summary: This article discusses the impact of alternative splicing on liver carcinogenesis and the development of malignant characteristics of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Understanding these impacts is crucial for developing novel therapeutic approaches that can manipulate the phenotype of cancer cells.
Article
Biotechnology & Applied Microbiology
Runzhi Huang, Zixuan Zheng, Shuyuan Xian, Jiayao Zhang, Jingyi Jia, Dianwen Song, Penghui Yan, Huabin Yin, Peng Hu, Xiaolong Zhu, Zongqiang Huang, Tong Meng, Jie Zhang
Summary: This study constructed a predictive model based on ASEs and explored their molecular mechanism in BLCA bone metastasis, proposing a hypothesis that the splicing events of ITGB4 are regulated by the splicing factor JUP and may play a key role in BLCA bone metastasis through the glycosphingolipid biosynthesis ganglio series pathway.
Review
Biochemistry & Molecular Biology
Debanwita Roy Burman, Shalini Das, Chandrima Das, Rahul Bhattacharya
Summary: Enhanced metastasis and disease recurrence contribute to the high mortality rates in cancer. Epithelial-Mesenchymal Transition (EMT) and alternative splicing play crucial roles in cancer invasiveness, drug resistance, and stem-like behavior. Splicing factors control the splicing alterations of genes like FGFR and CD44 during trans-differentiation, impacting cancer progression.
MOLECULAR BIOLOGY REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Yao-Jie Pan, Bo-wen Liu, Dong-Sheng Pei
Summary: This review summarizes alternative splicing (AS) events closely related to cancer progression and presents promising treatments based on AS for cancer therapy. Splicing events involved in biological processes, such as acquiring proliferative capacity, invasive properties, angiogenic features, shifting metabolic ability, and immune escape inclination are discussed. The review highlights the potential of spliceosome-targeted and antisense oligonucleotide technologies as novel strategies in tumor therapy. Additionally, bioinformatics applications based on AS are summarized for better prediction and elucidation of regulatory routines. The aim of this research is to provide a better understanding of complex AS events associated with cancer biology and reveal AS as a promising target for future cancer treatment.
DNA AND CELL BIOLOGY
(2022)
Article
Gastroenterology & Hepatology
Ming Zhang, Can Chen, Zequn Lu, Yimin Cai, Yanmin Li, Fuwei Zhang, Yizhuo Liu, Shuoni Chen, Heng Zhang, Shuhui Yang, Hui Gen, Yuan Jiang, Caibo Ning, Jinyu Huang, Wenzhuo Wang, Linyun Fan, Yi Zhang, Meng Jin, Jinxin Han, Zhen Xiong, Ming Cai, Jiuyang Liu, Chaoqun Huang, Xiaojun Yang, Bin Xu, Heng Li, Bin Li, Xu Zhu, Yongchang Wei, Ying Zhu, Jianbo Tian, Xiaoping Miao
Summary: This study provides a comprehensive functional analysis of splicing quantitative trait loci (sQTLs) in cancer and specifically in colorectal cancer (CRC). The researchers identified genetic variants that control messenger RNA splicing and examined their association with CRC risk. They also conducted biological experiments to investigate the potential mechanisms of these sQTLs and target genes. The study highlights the role of sQTLs in cancer susceptibility and suggests their potential as biomarkers and therapeutic targets.
Article
Pharmacology & Pharmacy
Naphannop Sereesongsaeng, James F. Burrows, Christopher J. Scott, Klaudia Brix, Roberta E. Burden
Summary: Our study found that CTSV has an impact on breast cancer cell proliferation, with depleted CTSV cells showing delayed progression through the G2/M phase of the cell cycle. Further investigation revealed that CTSV can regulate the expression levels of histones H3 and H4 in the nucleus by controlling the expression of their chaperone protein sNASP. We also discovered that CTSV is localized in the nuclear compartment of breast tumor cells and is required for cell cycle progression and histone stability.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Oncology
Jamal Elhasnaoui, Giulio Ferrero, Valentina Miano, Santina Cutrupi, Michele De Bortoli
Summary: This study reveals a novel mechanism of gene regulation mediated by estrogen receptor alpha in breast cancer cells, involving the control of RNA-binding protein expression and effects on isoform usage and alternative splicing. These regulatory mechanisms play a significant role in cell proliferation and epithelial-to-mesenchymal transition in breast cancer.
Article
Oncology
Pihua Han, Jingjun Zhu, Guang Feng, Zizhang Wang, Yanni Ding
Summary: This study identified survival-associated AS events and signatures that can help predict the survival outcomes of patients with BRCA. Additionally, constructed SF-AS networks in BRCA can reveal the underlying regulatory mechanisms in BRCA.
Article
Biochemistry & Molecular Biology
Jamal Elhasnaoui, Giulio Ferrero, Valentina Miano, Lorenzo Franchitti, Isabella Tarulli, Lucia Coscujuela Tarrero, Santina Cutrupi, Michele De Bortoli
Summary: This study found that ESRP1 is overexpressed in breast cancer patients, particularly in luminal BCs, and is correlated with estrogen receptor alpha levels. Analysis of genome-binding profiles revealed that ER alpha regulates the expression of ESRP1 and ESRP2 genes. Knocking down ESRP1/2 led to dysregulation of 754 genes, including alterations in alternative splicing events involved in cell signaling, metabolism, cell growth, and EMT. Functional network analysis identified RAC1 as the hub node affected by ESRP1/2 silencing in ER alpha+ BCs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
He Zhang, Baoai Han, Xingxing Han, Yuying Zhu, Hui Liu, Zhiyong Wang, Yanfen Cui, Ran Tian, Zicong Gao, Ruinan Tian, Sixin Ren, Xiaoyan Zuo, Jianfei Tian, Fei Zhang, Ruifang Niu
Summary: Recent evidence suggests that splicing factors (SFs) and alternative splicing (AS) play important roles in cancer progression. This study constructed SF-risk-models and AS-risk-models in different BRCA subtypes, providing potential multidimensional biomarkers for the diagnosis, prognosis, and treatment of BRCA. The functional roles of the selected SFs were found to be highly context-dependent among different BRCA subtypes.
FRONTIERS IN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Sudarshan R. Malla, Burkhard Krueger, Thomas Wartmann, Matthias Sendler, Ujjwal M. Mahajan, F. Ulrich Weiss, Franziska G. Thiel, Carina De Boni, Fred S. Gorelick, Walter Halangk, Ali A. Aghdassi, Thomas Reinheckel, Anna S. Gukovskaya, Markus M. Lerch, Julia Mayerle
CELLULAR AND MOLECULAR LIFE SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Alejandro Gomez-Auli, Larissa Elisabeth Hillebrand, Daniel Christen, Sira Carolin Guenther, Martin Lothar Biniossek, Christoph Peters, Oliver Schilling, Thomas Reinheckel
Summary: The study investigates cathepsin B-mediated secretome changes in breast cancer and highlights CREG1 as a key factor in the tumor microenvironment that can suppress malignant cell behavior.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Nezka Kavcic, Miha Butinar, Barbara Sobotic, Marusa Hafner Cesen, Ana Petelin, Lea Bojic, Tina Zavasnik Bergant, Andreja Bratovs, Thomas Reinheckel, Boris Turk
Article
Multidisciplinary Sciences
Ying Zhang, Genis Valentin Gese, Charlotte Conz, Karine Lapouge, Juergen Kopp, Tina Woelfle, Sabine Rospert, Irmgard Sinning
NATURE COMMUNICATIONS
(2020)
Review
Biochemistry & Molecular Biology
Lena Hoelzen, Maria Alejandra Parigiani, Thomas Reinheckel
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2020)
Article
Multidisciplinary Sciences
Ying Zhang, Evelina De Laurentiis, Katherine E. Bohnsack, Mascha Wahlig, Namit Ranjan, Simon Gruseck, Philipp Hackert, Tina Wolfle, Marina Rodnina, Blanche Schwappach, Sabine Rospert
Summary: The GET pathway aids in delivering tail-anchored proteins to the ER, with Get4/5 components probing near the ribosomal exit tunnel and recruiting Sgt2 upon emergence of client proteins to initiate the targeting phase of the pathway.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Junjun Ni, Juan Zhao, Xinwen Zhang, Thomas Reinheckel, Vito Turk, Hiroshi Nakanishi
Summary: The study found that Cathepsin H plays a critical role in the proteolytic maturation and stabilization of TLR3, which is necessary for IFN-beta production. CatH deficiency led to impaired TLR3/IFN-beta signaling, resulting in microglial cell death and astrogliosis/glial scar formation in the hippocampus following HI injury, thereby suppressing hippocampal atrophy.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Neurosciences
Tingting Zhang, Huan Du, Mariela Nunez Santos, Xiaochun Wu, Mitchell D. Pagan, Lianne Jillian Trigiani, Nozomi Nishimura, Thomas Reinheckel, Fenghua Hu
Summary: This study generated and characterized antibodies specific to each granulin peptide and found that the levels of individual granulin peptides are differently regulated in different tissues. The study also revealed variations in the levels of PGRN and granulin peptides in different brain regions, and showed that the changes in granulin A corresponded to stroke but not demyelination. Furthermore, deficiency of lysosomal proteases and prosaposin affected the ratios between individual granulin peptides.
MOLECULAR NEURODEGENERATION
(2022)
Review
Biochemistry & Molecular Biology
Thomas Reinheckel, Martina Tholen
Summary: For a long time, lysosomes were considered as organelles responsible for garbage disposal within the cell. Recent research, however, has shown that lysosomes also play a crucial role in integrating intracellular and extracellular signals. It has been found that lysosomal enzymes can be released in a way that is compatible with cellular survival, challenging the previous belief that impaired lysosomal membrane integrity leads to cell death. This review discusses the evidence and mechanisms by which lysosomal enzymes, particularly cathepsin proteases, reach unusual destinations within the cell.
Review
Pharmacology & Pharmacy
Gregory Hook, Thomas Reinheckel, Junjun Ni, Zhou Wu, Mark Kindy, Christoph Peters, Vivian Hook
Summary: This review evaluates the effects of deleting the CTSB gene on brain dysfunctions in neurological diseases and aging animal models. The findings suggest that CTSB gene knockout improves behavioral deficits, neuropathology, and biomarkers, supporting CTSB as a rational drug target for treating neurologic disorders.
PHARMACOLOGICAL REVIEWS
(2022)
Article
Oncology
Lena Hoelzen, Kerstin Syre, Jan Mitschke, Tilman Brummer, Cornelius Miething, Thomas Reinheckel
Summary: This article investigates the role of proteases in breast cancer progression and metastasis. By using genetic screens, the authors identify 252 protease genes involved in breast cancer cell growth, with 9 genes functionally validated. The study also reveals that environmental conditions influence breast cancer cell dependency on certain proteases.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Emilia Neuwirt, Giovanni Magnani, Tamara Cikovic, Svenja Woehrle, Larissa Fischer, Anna Kostina, Stephan Flemming, Nora J. Fischenich, Benedikt S. Saller, Oliver Gorka, Steffen Renner, Claudia Agarinis, Christian N. Parker, Andreas Boettcher, Christopher J. Farady, Rebecca Kesselring, Christopher Berlin, Rolf Backofen, Marta Rodriguez-Franco, Clemens Kreutz, Marco Prinz, Martina Tholen, Thomas Reinheckel, Thomas Ott, Christina J. Gross, Philipp J. Jost, Olaf Gross
Summary: The activation mechanisms of NOD-like receptor (NLR) protein-mediated inflammasomes were investigated. It was discovered that tyrosine kinase inhibitors (TKIs), including clinically approved drugs like imatinib and crizotinib, activated the NLRP3 inflammasome. These TKIs caused lysosomal swelling and damage, resulting in cell lysis and activation of NLRP3. This finding suggests a potential off-target effect of TKIs that may contribute to their clinical efficacy or adverse effects.
Article
Multidisciplinary Sciences
Claudio Bussi, Tiaan Heunis, Enrica Pellegrino, Elliott M. Bernard, Nourdine Bah, Mariana Silva Dos Santos, Pierre Santucci, Beren Aylan, Angela Rodgers, Antony Fearns, Julia Mitschke, Christopher Moore, James MacRae, Maria Greco, Thomas Reinheckel, Matthias Trost, Maximiliano G. Gutierrez
Summary: This study reveals that limited lysosomal damage leads to changes in the mitochondrial proteome and the modulation of macrophage immunometabolism. It shows that protease leakage from lysosomes triggers a cell death-independent proteolytic remodeling of the mitochondrial proteome in macrophages.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Lena Hoelzen, Jan Mitschke, Claudia Schoenichen, Maria Elena Hess, Sophia Ehrenfeld, Melanie Boerries, Cornelius Miething, Tilman Brummer, Thomas Reinheckel
Summary: This study suggests that proteases can act synergistically with PI3K inhibition in breast cancer cells, leading to enhanced therapeutic outcomes. Through a series of experiments, the researchers identified Usp7, Metap1, and Metap2 as key proteases that exhibit synthetic lethal effects when combined with PI3K inhibitors.
Article
Medicine, Research & Experimental
Lindsay B. Alcaraz, Aude Mallavialle, Timothee David, Danielle Derocq, Frederic Delolme, Cindy Dieryckx, Caroline Mollevi, Florence Boissiere-Michot, Joelle Simony-Lafontaine, Stanislas Du Manoir, Pitter F. Huesgen, Christopher M. Overall, Sophie Tartare-Deckert, William Jacot, Thierry Chardes, Severine Guiu, Pascal Roger, Thomas Reinheckel, Catherine Moali, Emmanuelle Liaudet-Coopman
Summary: This study identified a novel crosstalk between proteases and matricellular proteins in the tumor microenvironment through limited SPARC proteolysis, revealing a novel targetable 9-kDa bioactive SPARC fragment for new TNBC treatments. The research paves the way for developing strategies to target bioactive fragments from matricellular proteins in TNBC.