Article
Oncology
Hsin-Yi Chen, Shu-Jou Chan, Xinxin Liu, An-Chi Wei, Ru-In Jian, Kuan-Wei Huang, Yaw-Dong Lang, Jou-Ho Shih, Chun-Chieh Liao, Chiu-Lin Luan, Yu-Tung Kao, Shang-Yin Chiang, Pei-Wen Hsiao, Yuh-Shan Jou, Yunching Chen, Ruey-Hwa Chen
Summary: This study identifies the lncRNA Smyca as an oncogene that promotes poor prognosis in multiple cancer types. Smyca enhances tumor metabolic reprogramming, migration, invasion, cancer stemness, metastasis, and chemoresistance by potentiating TGF-beta/Smad signaling and c-Myc-mediated transcription. Targeting Smyca prevents metastasis and overcomes chemoresistance.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Review
Medicine, General & Internal
Masao Saitoh
Summary: Epithelial-mesenchymal transition (EMT) plays a crucial role in cancer progression, associated with invasion, metastasis, generation of tumor stem cells, and resistance to therapy. Transforming growth factor (TGF)-beta acts as a key mediator in the EMT process, initiating and maintaining EMT through signaling pathways and transcription factors.
Article
Pharmacology & Pharmacy
Saurabh Pal, Neha Singh, Indra Dev, Vineeta Sharma, Anjaneya Ayanur, Pankaj Ramji Jagdale, Kausar Mahmood Ansari
Summary: In this study, the mechanism involved in pro-fibrotic changes in the kidney after low-dose chronic exposure to PAT was investigated using in vitro and in vivo approaches. The results demonstrated that PAT exposure caused the generation of reactive oxygen species (ROS), activation of MAPKs and cJun/Fos signaling pathways, and induction of TGF-β(1) expression. Additionally, it was found that PAT-induced TGF-β(1) further activated the TGF-β(1)/smad signaling pathways and modulated the expression of slug and snail, leading to the regulation of pro-fibrotic molecules. The in vivo results also confirmed the kidney injury/toxicity effects of PAT exposure in rats.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mai Koizumi Ichikawa, Kaori Endo, Yuka Itoh, Asami Hotta Osada, Yujiro Kimura, Koichiro Ueki, Kunio Yoshizawa, Keiji Miyazawa, Masao Saitoh
Summary: The epithelial-mesenchymal transition (EMT) plays a crucial role in epithelial tumor progression. EMT transcription factors Snail and ZEB1/2 are key regulators of this transition. TGF-beta and active Ras signals induce the expression of Snail, while Ets1 and Ets2 contribute to the upregulation of both Snail and ZEB1/2. Ets1 is a crucial molecule for regulating Snail and ZEB1/2, and cancer progression is mediated through post-translational modification of the exon VII domain.
Review
Oncology
Valeria Ramundo, Giuliana Giribaldi, Elisabetta Aldieri
Summary: Metabolic changes in the tumor microenvironment play a critical role in cancer by affecting signaling pathways that control cellular metabolism. The deregulation of cancer metabolism is closely related to oxidative stress control and the involvement of cytokines like transforming growth factor beta (TGF-beta) in tumorigenesis and cancer progression. The crosstalk between TGF-beta and oxidative stress contributes significantly to tumorigenesis and cancer invasiveness by affecting redox imbalance and cellular metabolism.
Review
Cell Biology
Ji-Ung Jung, Ankita B. Jaykumar, Melanie H. Cobb
Summary: In this review, the role of WNK1 in tumor malignancy, metastasis, angiogenesis, and mesenchymal transition is discussed, providing evidence for its unique association with a subset of invasive cancers.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Immunology
Ruo Chen, Ke Wang, Zhuan Feng, Ming-Yang Zhang, Jiao Wu, Jie-Jie Geng, Zhi-Nan Chen
Summary: Inhibition of CD147 on T cells can slow down thymic aging and increase production of naive T cells by slowing the EMT process in TECs. This mechanism involves the interaction between T cells and TECs, leading to reduced adipocyte accumulation and potential strategies to hinder age-related thymic involution by inhibiting TGF beta and CD147.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Oncology
Li Wei, Naiyuan Shao, Ya Peng, Peng Zhou
Summary: The study revealed a correlation between high CTSS expression and glioma tissue grades, with CTSS inhibitor ZFL attenuating TGF-beta-induced invasive growth. Inhibition of CTSS reversed TGF-beta-induced epithelial-to-mesenchymal transition and restored the turnover of tight junction proteins, leading to decreased mobility of glioblastoma cells. Furthermore, the PI3K/AKT/mTOR pathway was found to be suppressed in the TGF-beta+ZFL groups, highlighting its importance in this process.
Article
Ophthalmology
Yi Chen, Binxin Wu, Jian Feng He, Jingyao Chen, Zi Wei Kang, Dandan Liu, Junjie Luo, Kexin Fang, Xiaoxu Leng, Haibin Tian, Jingying Xu, Caixia Jin, Jieping Zhang, Juan Wang, Jingfa Zhang, Qingjian Ou, Lixia Lu, Furong Gao, Guo-Tong Xu
Summary: This study successfully induced EMT in RPE cells through prolonged low-density culture, and found that the combination of the ROCK inhibitor Y27632 and the TGF-beta receptor inhibitor RepSox effectively suppressed and reversed the EMT process, maintaining the morphology and function of RPE cells and the retina. This combined therapy could be a new strategy for treating proliferative retinal diseases involving EMT of RPE cells.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Oncology
Bei Pu, Xu Zhang, Tengfeng Yan, Yuntao Li, Baohui Liu, Zhihong Jian, Omer Kamal Mahgoub, Lijuan Gu, Xiaoxing Xiong, Ning Zou
Summary: Recent studies have shown that MICAL2 plays a role in promoting proliferation and migration of glioblastoma through the TGF-beta/p-Smad2/EMT-like signaling pathway. Knockdown of MICAL2 can inhibit the growth and invasion abilities of glioblastoma cells. High MICAL2 expression predicts poor prognosis in GBM patients, making it a potential therapeutic target.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Xuecong Wang, Pieter Johan Adam Eichhorn, Jean Paul Thiery
Summary: TGF-beta signaling regulates embryonic development, wound-healing, and immune homeostasis, but it is altered during tumor progression, leading to enhanced epithelial cell plasticity and a reprogramming of epithelial cells into mesenchymal lineages through EMT. This contributes to increased carcinoma cell invasion, metastasis, and immune evasion.
SEMINARS IN CANCER BIOLOGY
(2023)
Article
Chemistry, Medicinal
Yue Ying Liu, Zhen Guo, Jing Ying Wang, Hui Min Wang, Jun Da Qi, Juan Ma, Hu-Ri Piao, Cheng Hua Jin, Xuejun Jin
Summary: Compounds targeting both ALK5 and p38α were synthesized and evaluated, with one compound, 13c, showing potential as an inhibitor in the treatment of human glioma.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Cheng-Yi Huang, Jenq-Lin Yang, Jih-Jung Chen, Shun-Ban Tai, Yu-Hsuan Yeh, Pei-Feng Liu, Ming-Wei Lin, Chih-Ling Chung, Chun-Lin Chen
Summary: The study showed that FQs inhibit MMP-9 expression in cancer cells, leading to a decrease in cell migration and invasion, demonstrating their potential value in cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Isabella Lurje, Nadine T. Gaisa, Ralf Weiskirchen, Frank Tacke
Summary: Fibrosis, a pathological scar tissue formation, can occur in various organs due to different etiologies and contributes to global morbidity and mortality. Common mechanisms involve sustained injury to parenchymal cells triggering a deregulated wound healing response. The transformation of fibroblasts into myofibroblasts with excessive extracellular matrix production is a hallmark of the disease, along with complex cellular interactions involving immune cells, endothelial cells, and parenchymal cells. Mediators such as growth factors, cytokines, and danger-associated molecular patterns play important roles in fibrosis across organs.
MOLECULAR ASPECTS OF MEDICINE
(2023)
Review
Oncology
Meng Lin, Jinmeng Liu, Fengping Zhang, Gaoxiu Qi, Shuqi Tao, Wenyuan Fan, Min Chen, Kang Ding, Fenghua Zhou
Summary: LRG1 plays a critical role in the proliferation, migration, and invasion of tumor cells and can serve as an early tumor and prognostic biomarker. Through the TGF-beta signaling pathway and other independent pathways, LRG1 regulates processes such as angiogenesis, epithelial-mesenchymal transition, and apoptosis, impacting the occurrence and development of tumors.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2022)
Article
Cell Biology
Angela Santoro, Thalia Vlachou, Lucilla Luzi, Giorgio Melloni, Luca Mazzarella, Errico D'Elia, Xieraili Aobuli, Cristina Elisabetta Pasi, Linsey Reavie, Paola Bonetti, Simona Punzi, Lucia Casoli, Arianna Sabo, Maria Cristina Moroni, Gaetano Ivan Dellino, Bruno Amati, Francesco Nicassio, Luisa Lanfrancone, Pier Giuseppe Pelicci
Article
Biochemistry & Molecular Biology
Alessandra Tesi, Stefano de Pretis, Mattia Furlan, Marco Filipuzzi, Marco J. Morelli, Adrian Andronache, Mirko Doni, Alessandro Verrecchia, Mattia Pelizzola, Bruno Amati, Arianna Sabo
Article
Gastroenterology & Hepatology
Andrea Bisso, Marco Filipuzzi, Gianni Paolo Gamarra Figueroa, Giulia Brumana, Francesca Biagioni, Mirko Doni, Giorgia Ceccotti, Nina Tanaskovic, Marco Jacopo Morelli, Vera Pendino, Fulvio Chiacchiera, Diego Pasini, Daniela Olivero, Stefano Campaner, Arianna Sabo, Bruno Amati
Article
Multidisciplinary Sciences
Megan J. Bywater, Deborah L. Burkhart, Jasmin Straube, Arianna Sabo, Vera Pendino, James E. Hudson, Gregory A. Quaife-Ryan, Enzo R. Porrello, James Rae, Robert G. Parton, Theresia R. Kress, Bruno Amati, Trevor D. Littlewood, Gerard Evan, Catherine H. Wilson
NATURE COMMUNICATIONS
(2020)
Article
Biochemistry & Molecular Biology
Paola Pellanda, Mattia Dalsass, Marco Filipuzzi, Alessia Loffreda, Alessandro Verrecchia, Virginia Castillo Cano, Hugo Thabussot, Mirko Doni, Marco J. Morelli, Laura Soucek, Theresia Kress, Davide Mazza, Marina Mapelli, Marie-Eve Beaulieu, Bruno Amati, Arianna Sabo
Summary: Eukaryotic transcription factors have both specific DNA sequence motif recognition and non-specific DNA-binding activity. Non-specific DNA binding is essential for engaging with genomic regulatory regions, while sequence recognition contributes to transcriptional activation by stabilizing Myc onto DNA and unexpectedly promoting its transcriptional activity. The seemingly pervasive genome interaction profiles detected by ChIP-seq actually encompass diverse DNA-binding modes driving defined, sequence-dependent transcriptional responses.
Article
Oncology
Giulio Donati, Micol Rava, Marco Filipuzzi, Paola Nicoli, Laura Cassina, Alessandro Verrecchia, Mirko Doni, Simona Rodighiero, Federica Parodi, Alessandra Boletta, Christopher P. Vellano, Joseph R. Marszalek, Giulio F. Draetta, Bruno Amati
Summary: MYC activity is closely correlated with gene expression signatures related to oxidative phosphorylation in DLBCL, sensitizing B cells to the ETC complex I inhibitor IACS-010759. The combination of BCL2 inhibitor venetoclax and IACS-010759 showed synergy in DHL with concurrent activation of MYC and BCL2, while in BCL2-negative lymphoma cells, the Mcl-1 inhibitor S63845 potentiated killing by IACS-010759. This suggests a novel therapeutic approach against aggressive, MYC-associated DLBCL variants.
MOLECULAR ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Chiara Ronchini, Sara Gandini, Sebastiano Pasqualato, Luca Mazzarella, Federica Facciotti, Marina Mapelli, Gianmaria Frige', Rita Passerini, Luca Pase, Silvio Capizzi, Fabrizio Mastrilli, Roberto Orecchia, Gioacchino Natoli, Pier Giuseppe Pelicci
Summary: In this study, we found that the probability of infection post-vaccination is significantly lower compared to natural infection, and the duration of infection is shorter. These findings are negatively correlated with circulating antibody levels.
Article
Biology
Nina Tanaskovic, Mattia Dalsass, Marco Filipuzzi, Giorgia Ceccotti, Alessandro Verrecchia, Paola Nicoli, Mirko Doni, Daniela Olivero, Diego Pasini, Haruhiko Koseki, Arianna Sabo, Andrea Bisso, Bruno Amati
Summary: Loss of Mga and PRC1.6 has no significant impact on Myc-induced lymphomagenesis in transgenic mice, but loss of Pcgf6 accelerates tumor formation. This suggests an unexpected tumor suppressor activity of Pcgf6 independent of Mga and PRC1.6.
LIFE SCIENCE ALLIANCE
(2022)
Review
Oncology
Giulio Donati, Bruno Amati
Summary: The MYC transcription factor plays a crucial role in tumor progression and therapeutic responses. Overexpression of MYC can lead to therapy resistance and create specific vulnerabilities in cancer cells that can be targeted by novel anticancer drugs.
MOLECULAR ONCOLOGY
(2022)
Article
Medicine, Research & Experimental
Giulio Donati, Paola Nicoli, Alessandro Verrecchia, Veronica Vallelonga, Ottavio Croci, Simona Rodighiero, Matteo Audano, Laura Cassina, Aya Ghsein, Giorgio Binelli, Alessandra Boletta, Nico Mitro, Bruno Amati
Summary: MYC is a key driver in multiple tumor types and can be targeted by drugs that suppress mitochondrial respiration. In this study, the mechanistic basis for the lethal interaction between MYC and respiratory complex I inhibitor IACS-010759 was unraveled. It was found that high-dose ascorbate synergized with IACS-010759 to kill MYC-overexpressing cells and improved therapeutic outcomes in B-cell lymphoma xenografts.
EMBO MOLECULAR MEDICINE
(2023)