Review
Pharmacology & Pharmacy
Rohit Siddhartha, Minal Garg
Summary: MMPs are a group of enzymes that play a crucial role in degrading proteins in the extracellular matrix and regulating cell signaling. Dysregulation of MMPs can lead to serious pathological conditions such as inflammation, uncontrolled cell growth, and cancer metastasis. Understanding the functions of MMPs has potential implications for cancer diagnosis, prognosis, and therapy.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2021)
Review
Oncology
Nadezhda V. Popova, Manfred Juecker
Summary: The extracellular matrix plays a critical role in cancer development and progression by influencing the behavior of cancer cells. Abnormal extracellular matrix directly promotes cancer cell proliferation, survival, migration, and differentiation, leading to the emergence of an oncogenic microenvironment.
Article
Genetics & Heredity
Fumiaki Takatsu, Ken Suzawa, Shuta Tomida, Yin Min Thu, Masakiyo Sakaguchi, Tomohiro Toji, Masayoshi Ohki, Shimpei Tsudaka, Keiichi Date, Naoki Matsuda, Kazuma Iwata, Yidan Zhu, Kentaro Nakata, Kazuhiko Shien, Hiromasa Yamamoto, Akiko Nakayama, Mikio Okazaki, Seiichiro Sugimoto, Shinichi Toyooka
Summary: CAF-derived POSTN plays a crucial role in tumor growth, migration, EMT induction, and drug resistance in NSCLC. Targeting CAF-secreted POSTN could be a potential therapeutic strategy for NSCLC.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2023)
Review
Oncology
Kellen Wright, Thuc Ly, Matthew Kriet, Andras Czirok, Sufi Mary Thomas
Summary: Cancer cells rely on the tumor microenvironment (TME) for growth and metastasis. Among the components of TME, cancer-associated fibroblasts (CAFs) play a crucial role. CAFs are heterogeneous and can remodel the microenvironment, as well as communicate with immune cells to aid in immune evasion. This review focuses on the factors and signaling pathways of CAFs.
Article
Medicine, Research & Experimental
Elmira Roshani Asl, Davoud Rostamzadeh, Pascal H. G. Duijf, Sahar Mafi, Behnaz Mansoori, Shirin Barati, William C. Cho, Behzad Mansoori
Summary: TP53 is the most frequently mutated gene in human cancer, encoding the tumor suppressor protein p53. Mutations in TP53 gene impair p53 function, alter intracellular signaling pathways, and promote cancer development. Recent evidence suggests that p53 mutations also affect the tumor microenvironment (TME), composed of various cell types, and influence cancer progression by fine-tuning the inflammatory TME and cell fate reprogramming. Understanding how TP53 mutations reshape TME can provide insights for therapeutic strategies against cancer.
Review
Biochemistry & Molecular Biology
Stephan Niland, Johannes A. Eble
Summary: The tumor microenvironment (TME) is a key focus in cancer research and treatment, involving various components including ECM and modifying enzymes. Cells within the TME interact with the ECM, influencing tumor progression through feedback mechanisms involving cellular receptors, cytokines, and exosomes. Matrix remodeling in the TME, particularly by matrix metalloproteinases (MMPs), plays a crucial role in modifying ECM barriers and releasing soluble ECM fragments that impact cells both within and outside the TME.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Physiology
Giulia Biffi, David A. Tuveson
Summary: Efforts to develop anti-cancer therapies have mainly targeted the epithelial compartment, but recent studies have shown the significant influence of cancer-associated fibroblasts (CAFs) in tumor progression. CAFs not only promote cancer cell proliferation, therapy resistance, and immune exclusion, but may also restrain tumor progression in certain contexts. Research on CAFs has focused on their heterogeneity, plasticity, and functions across different cancer types and states, as well as advancements in therapeutic strategies targeting CAFs currently undergoing preclinical and clinical evaluation.
PHYSIOLOGICAL REVIEWS
(2021)
Article
Oncology
Sieun Lee, Ji Hyung Hong, Jeong Seon Kim, Jung Sook Yoon, Sang Hoon Chun, Soon Auck Hong, Eun Ju Kim, Keunsoo Kang, Jihee Lee Kang, Yoon Ho Ko, Young-Ho Ahn
Summary: This study reveals that miR-196a promotes the migration and invasion of lung cancer cells by regulating ANXA1 and CCL2 in the tumor microenvironment. High expression of miR-196a is associated with poor prognosis in lung adenocarcinoma patients.
Article
Oncology
Yan Li, Ying Chen, Liyun Miao, Yongsheng Wang, Min Yu, Xin Yan, Qi Zhao, Hourong Cai, Yonglong Xiao, Guichun Huang
Summary: This study found that TNFSF4 secreted by cancer-associated fibroblasts under stress conditions can promote chemoresistance in lung adenocarcinoma by inhibiting apoptosis of tumor cells. This suggests a potential mechanism for the development of treatment resistance in lung cancer patients undergoing chemotherapy and radiotherapy.
Review
Biochemistry & Molecular Biology
Stephan Niland, Andrea Ximena Riscanevo, Johannes Andreas Eble
Summary: This review examines the current knowledge of the interplay of various MMPs in the context of cancer on the protein, subcellular, and cellular level, with a focus on MMP-14. It highlights the importance of a deeper understanding of functional mechanisms for the development of new prognostic and predictive markers, as well as targeted therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Engineering, Biomedical
Jiayun Wei, Jia Yao, Mengchao Yan, Ye Xie, Pinyan Liu, Yongcui Mao, Xun Li
Summary: The tumor microenvironment (TME) plays a crucial role in tumorigenesis, development, immune escape, drug resistance, and other processes. Matrix stiffness, an important mechanical feature in the TME, affects the fate of cancer cells and stromal cells. Studying matrix stiffness could lead to the development of more efficient and specialized treatments.
ACTA BIOMATERIALIA
(2022)
Review
Biochemistry & Molecular Biology
Eiman Elwakeel, Andreas Weigert
Summary: Activation of the tumor-associated stroma and the role of cancer-associated fibroblasts (CAFs) in shaping tumor development are crucial in breast cancer. Understanding the multiple functions of CAFs and developing intervention strategies are important for improving breast cancer therapy. Further research is needed to identify specific subsets of CAFs that can be targeted for therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biotechnology & Applied Microbiology
Maria V. Monteiro, Yu Shrike Zhang, Vitor M. Gaspar, Joao F. Mano
Summary: The combination of organ-on-a-chip platforms with additive manufacturing technologies offers a disruptive approach for upgrading cancer-on-a-chip systems. These hybrid platforms can create physiomimetic 3D models that better emulate tumor microenvironment elements and improve the predictability of therapeutics performance.
TRENDS IN BIOTECHNOLOGY
(2022)
Article
Oncology
Tongyan Liu, Chencheng Han, Panqi Fang, Zhifei Ma, Xiaoxiao Wang, Hao Chen, Siwei Wang, Fanchen Meng, Cheng Wang, Erbao Zhang, Guozhang Dong, Hongyu Zhu, Wenda Yin, Jie Wang, Xianglin Zuo, Mantang Qiu, Jinke Wang, Xu Qian, Hongbing Shen, Lin Xu, Zhibin Hu, Rong Yin
Summary: This study reveals that cancer-associated fibroblasts (CAFs) in lung adenocarcinoma (LUAD) primarily enhance the glutamine metabolism of cancer cells. They have identified a CAF-specific long noncoding RNA, LINC01614, which is packaged by CAF-derived exosomes and mediates the enhancement of glutamine uptake in LUAD cells. Mechanistically, LINC01614 directly interacts with ANXA2 and p65 to facilitate the activation of NF-kappa B, leading to the upregulation of the glutamine transporters SLC38A2 and SLC7A5 and enhancing the glutamine influx of cancer cells. Clinically, LINC01614 expression in CAFs is associated with the glutamine influx and poor prognosis of patients with LUAD. Blocking exosome-transmitted LINC01614 inhibits glutamine addiction and LUAD growth in vivo.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Review
Oncology
Pradip De, Jennifer Aske, Nandini Dey
Summary: This review explores how cancer-associated fibroblasts interact with various cells in the tumor microenvironment to support the development of resistance to cancer therapy. Understanding the role of cancer-associated fibroblasts in treatment resistance is crucial for designing effective strategies to counteract drug resistance and improve treatment outcomes.
Review
Cell Biology
Caroline Jane Ross, Igor Ulitsky
Summary: This review outlines the development and limitations of methods for discovering functional elements in long noncoding RNAs (lncRNAs), and discusses the main challenges in this field.
WILEY INTERDISCIPLINARY REVIEWS-RNA
(2022)
Article
Cell Biology
Noa Furth, Efrat Shema
Summary: Genome regulation is governed by the dynamics of chromatin modifications, and understanding the complexity of epigenetic combinations is crucial for normal genome regulation and cancer research. The development of novel methodologies has enabled the measurement and characterization of these combinations.
CURRENT OPINION IN GENETICS & DEVELOPMENT
(2022)
Article
Oncology
Xiaoya Li, Birgitta Elisabeth Michels, Oyku Ece Tosun, Janine Jung, Jolane Kappes, Susanne Ibing, Nishanth Belugali Nataraj, Shashwat Sahay, Martin Schneider, Angelika Woerner, Corinna Becki, Naveed Ishaque, Lars Feuerbach, Bernd Hessling, Dominic Helm, Rainer Will, Yosef Yarden, Karin Muller-Decker, Stefan Wiemann, Cindy Koerner
Summary: This study investigates the functions of miRNAs and their 5'isomiRs. The results show that three variants of miR-183-5p are highly expressed and regulate cell proliferation and invasion in different ways. Proteomic analysis reveals that miR-183-5p vertical bar+2 modulates the cell cycle by directly targeting E2F1. Gene set enrichment analysis suggests that the activity of E2F correlates with the expression of miR-183-5p. This study demonstrates that different isomiRs from the same pre-miRNA may have different functions, collectively contributing to the same phenotype.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Multidisciplinary Sciences
Saptaparna Mukherjee, Martino Maddalena, YiQing Lu, Sebastien Martinez, Nishanth Belugali Nataraj, Ashish Noronha, Sansrity Sinha, Katie Teng, Victoria Cohen-Kaplan, Tamar Ziv, Sharathchandra Arandkar, Ori Hassin, Rishita Chatterjee, Anna-Chiara Pirona, Michal Shreberk-Shaked, Anat Gershoni, Yael Aylon, Zvulun Elazar, Yosef Yarden, Daniel Schramek, Moshe Oren
Summary: The p53R273H mutant interacts with SQSTM1/p62 and promotes cancer cell migration and invasion in a p62-dependent manner by driving the proteasomal degradation of cell junction-associated proteins.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Ori Hassin, Nishanth Belugali Nataraj, Michal Shreberk-Shaked, Yael Aylon, Rona Yaeger, Giulia Fontemaggi, Saptaparna Mukherjee, Martino Maddalena, Adi Avioz, Ortal Iancu, Giuseppe Mallel, Anat Gershoni, Inna Grosheva, Ester Feldmesser, Shifra Ben-Dor, Ofra Golani, Ayal Hendel, Giovanni Blandino, David Kelsen, Yosef Yarden, Moshe Oren
Summary: The TP53 gene is frequently mutated in colorectal cancer (CRC) and different mutations have different impacts on cancer progression. Specifically, CRC tumors harboring R273 mutations have a higher likelihood of developing metastatic disease and a worse prognosis compared to those with R175 mutations. Furthermore, these R273 mutations are associated with the activation of oncogenic signaling pathways. This study highlights the importance of understanding the specific TP53 mutations in CRC for precision-based medicine.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Boris Slobodin, Urmila Sehrawat, Anastasia Lev, Daniel Hayat, Binyamin Zuckerman, Davide Fraticelli, Ariel Ogran, Amir Ben-Shmuel, Elad Bar-David, Haim Levy, Igor Ulitsky, Rivka Dikstein
Summary: Translation of SARS-CoV-2-encoded mRNAs is crucial for its propagation. The viral protein NSP1 inhibits translation and induces mRNA degradation, while viral mRNAs remain stable. A conserved RNA element in viral mRNAs confers resistance to NSP1-mediated translation inhibition. The 5' UTR of SARS-CoV-2 promotes cap-independent translation and expression of NSP1. These findings provide insights into the virus's propagation mechanism and potential therapeutic targets.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biotechnology & Applied Microbiology
Vadim Fedyuk, Nir Erez, Noa Furth, Olga Beresh, Ekaterina Andreishcheva, Abhijeet Shinde, Daniel Jones, Barak Bar Zakai, Yael Mavor, Tamar Peretz, Ayala Hubert, Jonathan E. Cohen, Azzam Salah, Mark Temper, Albert Grinshpun, Myriam Maoz, Aviad Zick, Guy Ron, Efrat Shema
Summary: This study developed a single-molecule imaging technique that can accurately and sensitively detect colorectal cancer in cell-free nucleosomes. By analyzing the epigenetics, DNA methylation, and cancer-specific protein biomarkers of plasma-isolated nucleosomes, the system allows for high-resolution detection of histone modifications and provides quantitative data on plasma proteins. The analysis showed high accuracy and sensitivity in detecting cancer, even at early stages, and could determine the tissue origin of tumors.
NATURE BIOTECHNOLOGY
(2023)
Review
Biotechnology & Applied Microbiology
Ori Hassin, Moshe Oren
Summary: Mutations in the TP53 gene are common in cancer, but restoring p53 functionality has been considered impossible for a long time. However, recent years have seen promising developments in p53-based therapy, including improved strategies and novel approaches. Small molecules that protect or restore p53 function are gaining interest, along with tailored drugs for specific p53 mutants. Additionally, gene therapy and immunotherapy are being reconsidered. However, significant challenges remain.
NATURE REVIEWS DRUG DISCOVERY
(2023)
Correction
Multidisciplinary Sciences
Yael Aylon, Noa Furth, Giuseppe Mallel, Gilgi Friedlander, Nishanth Belugali Nataraj, Meng Dong, Ori Hassin, Rawan Zoabi, Benjamin Cohen, Vanessa Drendel, Tomer Meir Salame, Saptaparna Mukherjee, Nofar Harpaz, Randy Johnson, Walter E. Aulitzky, Yosef Yarden, Efrat Shema, Moshe Oren
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Jubina Balan Venghateri, Bareket Dassa, David Morgenstern, Michal Shreberk-Shaked, Moshe Oren, Benjamin Geiger
Summary: This study investigates the involvement of YAP and TAZ, key regulators of the Hippo pathway, in invadopodia formation and matrix degradation. Knockdown or inhibition of YAP and TAZ enhances matrix degradation and invadopodia formation in multiple cancer cell lines, while overexpression suppresses these processes. Proteomic and transcriptomic analysis reveals changes in levels of key invadopodia-associated proteins. These findings suggest that YAP and TAZ act as negative regulators of invadopodia formation by reducing levels of essential invadopodia components. Understanding the molecular mechanisms of invadopodia formation in cancer invasion may lead to the identification of novel therapeutic targets.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Noa Gil, Rotem Ben-Tov Perry, Zohar Mukamel, Alex Tuck, Marc Buhler, Igor Ulitsky
Summary: This study investigates a lncRNA (Meteor) that is transcribed near the gene encoding EOMES and finds that transcription elongation through the Meteor locus is necessary for Eomes activation in mouse embryonic stem cells and is associated with mesoderm differentiation. The study also reveals that a distinct DNA element within the locus is required for suppressing Eomes expression following neuronal differentiation.
Review
Genetics & Heredity
Alan Monziani, Igor Ulitsky
Summary: This review summarizes past and recent evidence that noncoding snoRNA host genes (ncSNHGs) form a defined subclass among the plethora of lncRNAs and discusses future research that can further elucidate their biological relevance.
TRENDS IN GENETICS
(2023)
Article
Cell Biology
Rotem Ben-Tov Perry, Michael Tsoory, Michael Tolmasov, Igor Ulitsky
Summary: In this study, the researchers found that the long noncoding RNA Silc1 is important for spatial learning in the hippocampus, and it activates the cis-regulated gene Sox11 and induces a transcriptional program associated with neuronal growth, thus participating in neuronal plasticity.
Meeting Abstract
Oncology
Arunachalam Sekar, Nishanth Belugali Nataraj, Yosef Yarden
Meeting Abstract
Oncology
Yael Aylon, Noa Furth, Giuseppe Mallel, Nishanth Nataraj, Gilgi Friedlander, Ori Hassan, Rawan Zoabi, Benjamin Cohen, Tomer Salame, Saptaparna Mukherjee, Randy Johnson, Efrat Shema, Moshe Oren