Article
Cell Biology
Ting Peng, Shitong Lin, Yifan Meng, Peipei Gao, Ping Wu, Wenhua Zhi, Wencheng Ding, Canhui Cao, Peng Wu
Summary: This study investigated the expression level and functional mechanism of LOXL2 in cervical cancer using bioinformatics and experimental methods. The results showed that LOXL2 was significantly upregulated in cervical cancer and promoted the malignant transformation of cervical cancer cells through mediation of EMT. Additionally, a small molecule inhibitor of LOXL2 was found to reverse the LOXL2-induced EMT process and decrease the invasive ability of cervical cancer.
Review
Biochemistry & Molecular Biology
Sandra Ferreira, Nuno Saraiva, Patricia Rijo, Ana S. Fernandes
Summary: LOX and LOXL2 are amine oxidases that catalyze cross-linking reactions of elastin and collagen in connective tissue, with LOXL2 showing high expression in certain tumors. Inhibition of LOX and LOXL2 is considered a promising strategy for preventing metastasis and invasion of breast cancer. Novel synthetic compounds acting as selective inhibitors for LOX/LOXL2 or dual LOX/LOXL inhibitors have been developed, showing potential for effective therapeutic approaches in breast cancer treatment.
Article
Biochemistry & Molecular Biology
Pilar Eraso, Maria J. Mazon, Victoria Jimenez, Patricia Pizarro-Garcia, Eva P. Cuevas, Jara Majuelos-Melguizo, Jesus Morillo-Bernal, Amparo Cano, Francisco Portillo
Summary: Lysyl oxidase-like 2 (LOXL2) is known as an extracellular enzyme involved in extracellular matrix remodeling, but recent research reveals its intracellular functions in gene transcription, development, differentiation, proliferation, migration, cell adhesion, angiogenesis, and cancer progression. LOXL2 is also capable of inducing epithelial-to-mesenchymal transition (EMT), the first step in metastasis. Through the analysis of LOXL2's nuclear interactome, this study identifies its interaction with numerous RNA-binding proteins (RBPs) involved in RNA metabolism. Gene expression analysis and computational identification of RBPs' targets further suggest six candidates as LOXL2 substrates, warranting future mechanistic analysis. These findings propose novel functions of LOXL2 in tumorigenesis.
Article
Cell Biology
Haoyue Hu, Jing Ma, Zhiju Li, Ziling Ding, Wenqian Chen, You Peng, Zixin Tao, Lu Chen, Manling Luo, Chichiu Wang, Xuefei Wang, Jing Li, Mei Zhong
Summary: This study further elucidates the role of cyclophilin A (CyPA) in preeclampsia (PE). Through analysis of mouse placentae, it was found that CyPA increased extracellular matrix (ECM) proteins and inhibited genes involved in epithelial-mesenchymal transition (EMT) through the TGF-13/Smad3 signaling pathway. Cell models were used to demonstrate that CyPA regulates the levels of ECM-related proteins and the EMT process through the TGF-13/Smad3 pathway. SERPINH1 was identified as a potential CyPA-binding protein and was found to be upregulated in the placentae of PE. Silencing SERPINH1 expression reversed the upregulation of ECM proteins and inhibition of EMT induced by CyPA overexpression.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2022)
Article
Plant Sciences
Xiang-Zhen Fan, Yu-Fei Chen, Shi-Bing Zhang, Dan-Hua He, Su-Fen Wei, Qi Wang, Hua-Feng Pan, Yong-Qiang Liu
Summary: This study demonstrated that the ethanol extract of Centipeda minima (ECM) in combination with DNA-crosslinking agents exhibited synergistic cytotoxic effects against non-small cell lung cancer (NSCLC) cells by inhibiting the FA pathway protein FANCD2. ECM decreased DNA damage-induced monoubiquitination and nuclear foci formation of FANCD2, sensitizing NSCLC cells to CDDP or MMC-induced DNA damage and apoptosis. Additionally, ECM attenuated CDDP-mediated S-phase arrest and enhanced the anticancer effects of CDDP in both in vitro and in vivo experiments.
Article
Medicine, Research & Experimental
Cheng-Wei Huang, Shih-Yi Lee, Tzu-Tang Wei, Yueh-Hsiung Kuo, Shao-Tung Wu, Hui-Chun Ku
Summary: This study demonstrates that CAEA protects against I/R-induced renal remodeling by inhibiting EMT and reducing inflammatory reactions, potentially by targeting TGFBRI.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Biotechnology & Applied Microbiology
Fang Cheng, Fuji Yang, Yanjin Wang, Jing Zhou, Hui Qian, Yongmin Yan
Summary: This study investigates the efficacy and underlying mechanisms of human umbilical cord-derived exosomes (MSC-ex) in LOXL2 inhibition of liver fibrosis. It was found that MSC-ex could suppress LOXL2 expression through exosomal miR-27b-3p-mediated YAP down-regulation, thus delaying the progression of CCl4-induced liver fibrosis. These findings improve our understanding of the role of MSC-ex in liver fibrosis alleviation and provide new opportunities for clinical treatment.
JOURNAL OF NANOBIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sofia Spataro, Concetta Guerra, Andrea Cavalli, Jacopo Sgrignani, Jonathan Sleeman, Lina Poulain, Andreas Boland, Leonardo Scapozza, Solange Moll, Marco Prunotto
Summary: CEMIP, also known as KIAA1199 or HYBID, is a protein involved in the depolymerization of hyaluronic acid and has been shown to play a key role in tumor progression and various inflammatory diseases. Despite its association with these diseases, the biology of CEMIP remains elusive. This review article summarizes the scientific evidence regarding its structure, function, and expression, aiming to shed light on the protein's role in inflammation-related conditions.
Review
Biochemistry & Molecular Biology
Jelena Radic, Bojana Kozik, Ivan Nikolic, Ivana Kolarov-Bjelobrk, Tijana Vasiljevic, Bojana Vranjkovic, Sanja Despotovic
Summary: LOXL2, a copper-dependent amine oxidase, is a promising therapeutic target in hepatocellular carcinoma (HCC) due to its association with aggressive phenotype and poor prognosis. This review focuses on understanding the mechanisms by which LOXL2 regulates multiple oncogenic functions in HCC, including modulation of the tumor microenvironment, formation of premetastatic niches, and epithelial-mesenchymal transition. The complex interplay between LOXL2 and hypoxia, angiogenesis, and vasculogenic mimicry in HCC is also highlighted. Additionally, the review summarizes the current LOXL2 inhibitors and their potential in precision treatment of HCC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Philip A. P. Brudnicki, Matthew A. Gonsalves, Stephen M. Spinella, Laura J. Kaufman, Helen H. Lu
Summary: This study aims to fabricate a collagen-like extracellular matrix (ECM) analog using green electrospinning methods for tissue culture and disease research. The results demonstrate that by optimizing crosslinking and using the green electrospinning solvent acetic acid, collagen-like mesh structures with nano- and micro-scale cues and continuous fibrous architecture can be produced, and they exhibit stability in both dry and wet conditions. These collagen-like mesh structures support the in vitro expansion of cells and the production of mineralized matrix.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tianxiao Sun, Haihua Li, Yan Zhang, Guixin Xiong, Yuerun Liang, Fang Lu, Rong Zheng, Qi Zou, Jiejie Hao
Summary: In this study, it was found that DGM could inhibit TGF-beta 1-induced EMT in A549 cells and bleomycin-induced pulmonary fibrosis in rats. Furthermore, DGM treatment improved lung function, reduced lung inflammation and fibrosis, and decreased collagen deposition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Vincenzo Condello, Filomena Cetani, Maria Denaro, Liborio Torregrossa, Elena Pardi, Paolo Piaggi, Simona Borsari, Anello Marcello Poma, Lucia Anna Muscarella, Paolo Graziano, Maria Grazia Chiofalo, Andrea Repaci, Giovanni Tallini, Francesco Boi, Gabriele Materazzi, Fulvio Basolo, Claudio Marcocci
Summary: Parathyroid carcinoma (PC) is a rare and aggressive malignancy of the endocrine system, with uncertain diagnosis often requiring evidence of local invasion or secondary spread. Molecular markers play an important role in improving diagnostic accuracy. Analysis of gene expression profiles in different parathyroid tumors revealed specific molecular signatures associated with metastatic behavior and potential diagnostic markers for clinical practice.
ENDOCRINE-RELATED CANCER
(2021)
Article
Developmental Biology
Xin Sun, Sophia Malandraki-Miller, Tahnee Kennedy, Elad Bassat, Konstantinos Klaourakis, Jia Zhao, Elisabetta Gamen, Joaquim Miguel Vieira, Eldad Tzahor, Paul R. Riley
Summary: During heart development, epicardial cells undergo epithelial-mesenchymal transition (EMT) and migrate into myocardium, supporting organ growth. Agrin, a proteoglycan associated with extracellular matrix, is crucial for regulating epicardial EMT and basement membrane integrity, impacting heart development significantly.
Review
Immunology
Liam T. Caven, Rey A. Carabeo
Summary: Ocular, genital, and anogenital infections caused by Chlamydia trachomatis are often associated with scar formation. In cases of chronic or repeated infections in the female genital tract, fibrosis of the fallopian tubes can lead to ectopic pregnancy or infertility. The underlying mechanisms of Chlamydia-associated scarring are still under investigation.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Engineering, Biomedical
Long Zhao, Zhen Shi, Xiuli Sun, Yaoyao Yu, Xin Wang, Hongwei Wang, Tan Li, Hengrui Zhang, Xiaoyu Zhang, Fuyan Wang, Xia Qi, Rui Cao, Lixin Xie, Qingjun Zhou, Weiyun Shi
Summary: This study developed a novel ion-activated bioadhesive hydrogel for repairing large corneal defects, which demonstrated good transparency, biocompatibility, adhesion, and promoted rapid regeneration of corneal tissues.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Anatomy & Morphology
Ayalur R. Subbalakshmi, Sarthak Sahoo, Kuheli Biswas, Mohit Kumar Jolly
Summary: Epithelial-mesenchymal plasticity plays a crucial role in aggressive tumor progression, and cells in hybrid epithelial/mesenchymal phenotype exhibit greater aggressiveness. The study reveals that SLUG can stabilize cells in the hybrid epithelial/mesenchymal phenotype, functioning as a phenotypic stability factor. This finding has important implications for understanding metastasis mechanisms.
CELLS TISSUES ORGANS
(2023)
Article
Biochemistry & Molecular Biology
Veronika te Boekhorst, Liying Jiang, Marius Mahlen, Maaike Meerlo, Gina Dunkel, Franziska C. Durst, Yanjun Yang, Herbert Levine, Boudewijn M. T. Burgering, Peter Friedl
Summary: This article studies the molecular mechanisms of cancer cell invasion and metastasis under hypoxic conditions and identifies calpain-2 as a key regulator of the transition from collective to amoeboid dissemination in breast and head and neck carcinoma cells. The study reveals that hypoxia induces calpain-2-mediated amoeboid conversion by deactivating beta 1 integrins. Targeted intervention of calpain-2 activity can restore normal cell phenotype and prevent lung metastasis.
Article
Biochemistry & Molecular Biology
Shubham Tripathi, Sumitabha Brahmachari, Jose N. Onuchic, Herbert Levine
Summary: Multiple RNA polymerases (RNAPs) transcribing a gene can exhibit collective behavior, where the transcription elongation rate increases with the rate of transcription initiation. Recent studies suggest that even RNAPs separated by long distances can cooperate by modifying the DNA segment under transcription. This theoretical model incorporates the mechanical coupling between RNAP translocation and DNA torsional response, and stochastic simulations demonstrate DNA supercoiling-mediated long-range cooperation between co-transcribing RNAPs.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biophysics
Anish Hebbar, Ankush Moger, Kishore Hari, Mohit Kumar Jolly
Summary: The study found that multistable EMP networks are structurally and dynamically more robust compared to random networks, determined by the balance of positive and negative feedback loops embedded in the networks. By measuring the number and length of negative and positive feedback loops, the robustness of these networks can be explained, allowing for comparison across different sizes of networks without simulating dynamics.
BIOPHYSICAL JOURNAL
(2022)
Article
Anatomy & Morphology
Burhanuddin Sabuwala, Kishore Hari, Abhishek Shanmuga Vengatasalam, Mohit Kumar Jolly
Summary: Multistability is important in biological systems and can be achieved through positive feedback loops. This study investigates the bistability characteristics of mutual inhibition, mutual activation, and self-activation loops. The results show that mutual inhibition-based architecture provides discrete and robust control, multistability, and coordinated expression among multiple genes compared to mutual activation-based architecture. A combination of mutual inhibition and mutual activation architectures is proposed to improve coordination and multistability. This research improves our understanding of control structures in cell-fate decisions and provides insights for controlled decision-making in synthetic systems.
CELLS TISSUES ORGANS
(2023)
Article
Multidisciplinary Sciences
Sharaj Kunjar, Ariana Strandburg-Peshkin, Helge Giese, Pranav Minasandra, Sumantra Sarkar, Mohit Kumar Jolly, Nico Gradwohl
Summary: Consensus decision-making in social groups is influenced by communication links that determine information exchange. This study shows that strategically adjusting communication links can bias group-level outcomes and help achieve consensus, but strong preferences can lead to non-consensus outcomes.
ROYAL SOCIETY OPEN SCIENCE
(2023)
Article
Oncology
Viola Hedrich, Kristina Breitenecker, Gregor Ortmayr, Franziska Pupp, Heidemarie Huber, Doris Chen, Sarthak Sahoo, Mohit Kumar Jolly, Wolfgang Mikulits
Summary: This study identified PRAME as a target gene of the Gas6/Axl signaling pathway in hepatocellular carcinoma. PRAME promotes dedifferentiation, epithelial-to-mesenchymal transition, and invasion in liver cancer cells. The expression of PRAME is associated with an unfavorable prognosis in HCC patients.
Review
Chemistry, Multidisciplinary
Seemadri Subhadarshini, Joel Markus, Sarthak Sahoo, Mohit Kumar Jolly
Summary: Epithelial-mesenchymal plasticity (EMP) is a crucial factor in cancer metastasis and therapeutic resistance, allowing cancer cells to alter their characteristics along the epithelial-mesenchymal spectrum. Single-cell studies have provided valuable insights into the dynamics of EMP, showing the heterogeneity of hybrid epithelial/mesenchymal phenotypes and their impact on patient survival.
Article
Cell Biology
Shinjinee Sengupta, Namrata Singh, Ajoy Paul, Debalina Datta, Debdeep Chatterjee, Semanti Mukherjee, Laxmikant Gadhe, Jyoti Devi, Yeshwanth Mahesh, Mohit Kumar Jolly, Samir K. Maji
Summary: The study found a strong correlation between p53 amyloid load and cancer grades. Both mutant and wild-type p53 were capable of forming amyloids in cancer tissues. Furthermore, the p53 amyloids sequestered higher amounts of related proteins, suggesting a potential mechanism for loss of tumor-suppressive function and gain of oncogenic function in cancer progression.
JOURNAL OF CELL SCIENCE
(2023)
Review
Physics, Multidisciplinary
Federico Bocci, Dongya Jia, Qing Nie, Mohit Kumar Jolly, Jose Onuchic
Summary: The last decade has seen a rise in theoretical and computational models used to describe complex gene regulatory networks and their dynamics, which can result in multistable and heterogeneous cell populations. The application of theoretical modeling in genetic and biochemical circuits has become more widespread, with theoreticians incorporating concepts from statistical physics, non-linear dynamics, and network theory. This review provides an overview of important methodologies in the field, discusses current and future challenges, offers hands-on tutorials for solving and simulating biological system models, and presents concrete examples for theoreticians interested in this fast-developing field.
REPORTS ON PROGRESS IN PHYSICS
(2023)
Article
Mathematical & Computational Biology
Kishore Hari, William Duncan, Mohammed Adil Ibrahim, Mohit Kumar Jolly, Breschine Cummins, Tomas Gedeon
Summary: Mathematical modeling of gene regulatory networks (GRN) is challenging due to parameter dependence and lack of reliable experimental parameters. This study compares two approaches, RACIPE and DSGRN, for describing GRN dynamics across unknown parameters and finds agreement in simulation and predictions for cellular decision making. The observation is important as DSGRN parameter domains accurately predict ODE model dynamics within a biologically reasonable range of parameters.
NPJ SYSTEMS BIOLOGY AND APPLICATIONS
(2023)
Review
Computer Science, Interdisciplinary Applications
Maalavika Pillai, Emilia Hojel, Mohit Kumar Jolly, Yogesh Goyal
Summary: Computational models and tools have been used to understand the origins and nature of non-genetic heterogeneity in cancer, which has significant clinical implications. Non-genetic heterogeneity is increasingly associated with therapy resistance and metastasis in cancer. Identifying the origins of non-genetic heterogeneity is crucial for making clinical breakthroughs.
NATURE COMPUTATIONAL SCIENCE
(2023)
Article
Multidisciplinary Sciences
Paras Jain, Sophia Corbo, Kulsoom Mohammad, Sarthak Sahoo, Santhalakshmi Ranganathan, Jason T. George, Herbert Levine, Joseph Taube, Michael Toneff, Mohit Kumar Jolly
Summary: Epithelial-mesenchymal transition (EMT) and its reverse mesenchymal-epithelial transition (MET) play crucial roles in embryonic development, wound healing, and cancer metastasis. While short-term EMT induction can lead to reversible phenotypic changes, long-term EMT induction is often associated with irreversibility. In this study, we demonstrate that the phenotypic changes observed in MCF10A cells during long-term EMT induction by TGF-beta can in fact have longer timescales of reversibility. We also propose a mathematical model that explains how the epigenetic memory gained during long-term EMT induction can slow down the recovery to the epithelial state after TGF-beta withdrawal.
JOURNAL OF THE ROYAL SOCIETY INTERFACE
(2023)
Article
Oncology
Manas Sehgal, Soundharya Ramu, Joel Markus Vaz, Yogheshwer Raja Ganapathy, Srinath Muralidharan, Sankalpa Venkatraghavan, Mohit Kumar Jolly
Summary: This study investigates the relationship between gene expression patterns and phenotypic plasticity and heterogeneity in colorectal cancer (CRC). The results demonstrate the interconnectedness between different Consensus Molecular Subtypes (CMS) of CRC and specific phenotypes such as epithelial and mesenchymal characteristics. Additionally, the study reveals correlations between metabolic pathways and phenotypic scores, as well as between PD-L1 activity and mesenchymal phenotype. Single-cell RNA sequencing analysis further confirms the heterogeneity of different CMS subtypes. These findings have important implications for understanding CRC heterogeneity and developing targeted therapies.
TRANSLATIONAL ONCOLOGY
(2024)