Review
Pharmacology & Pharmacy
Fangfang Liu, Qiong Wu, Zigang Dong, Kangdong Liu
Summary: Integrins are crucial for cell adhesion and play a significant role in cell migration and tissue homeostasis. Abnormal activation of integrins has been linked to tumor formation, growth, and metastasis, making them attractive targets for cancer therapeutics.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Oncology
Yixi Yuan, Hongyan Zhang, Danni Li, Ying Li, Fengzhan Lin, Yanzhi Wang, Hui Song, Xu Liu, Feng Li, Jian Zhang
Summary: This article provides a systematic overview of the important role of PAK4 in cancer, including its structure, localization, expression and aberration, upstream regulators, and key functions in cancer cell proliferation, invasion and metastasis, angiogenesis, metabolism reprogram-ming, and immune escape. In addition, the existing small molecule PAK4 inhibitors and their potential applications in cancer treatment are discussed.
Review
Oncology
Meilan Hu, Fule He, Erik W. Thompson, Kostya (Ken) Ostrikov, Xiaofeng Dai
Summary: The article aims to explore the intrinsic connections between lysine acetylation and cancer properties, and propose novel modalities such as combining histone deacetylase inhibitors with cold atmospheric plasma as precision onco-therapies.
Review
Biotechnology & Applied Microbiology
R. J. Slack, S. J. F. Macdonald, J. A. Roper, R. G. Jenkins, R. J. D. Hatley
Summary: Integrins play crucial roles in cell adhesion and signaling, making them potential therapeutic targets. This review discusses the challenges and development of integrin inhibitors, particularly those targeting integrins with an alpha v-subunit. Opportunities exist for learning from previous trials and exploring new modalities in integrin drug design.
NATURE REVIEWS DRUG DISCOVERY
(2022)
Review
Biochemistry & Molecular Biology
Juliana Calheiros, Vincenzo Corbo, Lucilia Saraiva
Summary: Pancreatic cancer (PC) is associated with (epi)genetic and microenvironmental alterations, which negatively affect treatment outcomes. Targeting BRCA1/2 and TP53 deficiencies has been explored as promising therapeutic options. Mutations in p53 and dysfunctions in DNA repair-related genes, such as BRCA1/2, play a role in the aggressiveness and therapy resistance of PC. Therefore, personalized therapy targeting defective BRCAs and p53 pathways is crucial for overcoming PC resistance.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2023)
Article
Oncology
Qian Wang, Pengfei Yu, Chaoxu Liu, Xianli He, Gang Wang
Summary: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death worldwide, and enhanced mitochondrial fragmentation (MF) is associated with poor prognosis in HCC patients. Although MF activates certain immune cells, it decreases the number and cytotoxicity of natural killer cells in the HCC immune microenvironment, leading to immune escape. Moreover, MF contributes to maintaining stemness by promoting the asymmetric division of liver cancer stem cells. MF may promote tumor progression through autophagy, oxidative stress, and metabolic reprogramming.
Article
Oncology
Dan Du, Jing He, Chenxi Ju, Chang Wang, Hongle Li, Fucheng He, Mingxia Zhou
Summary: N7-methylguanosine (m7G) methylation is one of the most common RNA modifications in eukaryotes, and its biological functions in human diseases are largely unknown. Recent advances in high-throughput technologies have shown that m7G modification plays a critical role in cancer initiation and progression, and targeting m7G regulators may provide new possibilities for cancer diagnoses and interventions. This review summarizes various detection methods for m7G modification, recent advances in m7G modification and tumor biology, and provides an outlook on diagnosing and treating m7G-related diseases.
Article
Biochemistry & Molecular Biology
Fiorella Faienza, Federica Polverino, Girish Rajendraprasad, Giacomo Milletti, Zehan Hu, Barbara Colella, Deborah Gargano, Flavie Strappazzon, Salvatore Rizza, Mette Vixo Vistesen, Yonglun Luo, Manuela Antonioli, Valentina Cianfanelli, Caterina Ferraina, Gian Maria Fimia, Giuseppe Filomeni, Daniela De Zio, Joern Dengjel, Marin Barisic, Giulia Guarguaglini, Sabrina Di Bartolomeo, Francesco Cecconi
Summary: AMBRA1 is a key factor for nervous system development, primarily associated with autophagy and cell proliferation control. This study reveals that AMBRA1 is phosphorylated during mitosis and is critical for spindle function and orientation, driven by NUMA1 protein. The localization and dynamics of NUMA1 are dependent on AMBRA1 presence, phosphorylation, and binding ability. These findings suggest an additional role of AMBRA1 in tissue morphogenesis and differentiation, which could have implications for development and cancer oncogenesis.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Oncology
Rafael Rosell, Andres Felipe Cardona, Oscar Arrieta, Andres Aguilar, Masaoki Ito, Carlos Pedraz, Jordi Codony-Servat, Mariacarmela Santarpia
Summary: EGFR mutations in lung adenocarcinoma are common driver mutations, and while EGFR TKIs can extend survival, they can also lead to therapeutic resistance and progression. Research focuses on managing the acquisition of EGFR TKI-resistant mutations, but basic principles of cancer evolution have not been fully considered in clinical trials.
BRITISH JOURNAL OF CANCER
(2021)
Review
Gastroenterology & Hepatology
Manish Manrai, T. V. S. V. G. K. Tilak, Saurabh Dawra, Sharad Srivastava, Anupam Singh
Summary: Pancreatic carcinoma is a major cause of cancer-related deaths globally, with surgery and adjuvant chemotherapy being the current standard of care. Recent advancements in neoadjuvant therapy and chemoradiotherapy have shown promise for resectable and borderline resectable PC. Novel therapeutic strategies and targeted agents are on the horizon as our understanding of tumor biology, genetics, and microenvironment improves.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Review
Chemistry, Multidisciplinary
Yujia Hao, Haoyue Song, Zilan Zhou, Xiaohang Chen, Huifei Li, Yuan Zhang, Jie Wang, Xiuyun Ren, Xing Wang
Summary: Extracellular vesicles (EVs) are important vehicles for intercellular communication, with different physiological and pathological effects, and can be used as biological therapeutic agents. In some cases, the release of EVs can exacerbate disease progression, while inhibition may delay disease development.
JOURNAL OF CONTROLLED RELEASE
(2021)
Review
Biochemistry & Molecular Biology
Haihua Wang, Weiyuan Wang, Songqing Fan
Summary: Nasopharyngeal carcinoma is a malignant tumor with specific ethnic and geographical distribution characteristics. Recent studies have shown that long non-coding RNAs play important regulatory roles in the development of nasopharyngeal carcinoma. In-depth understanding of abnormal lncRNAs may provide new insights into the pathogenesis of nasopharyngeal carcinoma and offer new approaches for early diagnosis and treatment.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Xi Kang, Weilin Li, Weixin Liu, Han Liang, Jingyu Deng, Chi Chun Wong, Sinan Zhao, Wei Kang, Ka Fai To, Philip Wai Yan Chiu, Guiying Wang, Jun Yu, Enders Kwok Wai Ng
Summary: This study identified LIMK1 as a key promoter of gastric cancer peritoneal metastasis and suggested dabrafenib as a potential therapeutic target. The findings showed that targeting LIMK1 with dabrafenib could inhibit migration and invasion of gastric cancer cells in vitro and prevent metastasis in vivo, by suppressing phosphorylation of cofilin.
Review
Cell & Tissue Engineering
Chuchao Zhou, Boyu Zhang, Yanqing Yang, Qiong Jiang, Tianyu Li, Jun Gong, Hongbo Tang, Qi Zhang
Summary: Wound healing is a complex process involving hemostasis, inflammation, proliferation, and tissue remodeling. Mesenchymal stem cell-derived exosomes (MSC-exos) have lower immunogenicity and high biological activity, and play a role in regulating the behavior of various skin cells. This study focuses on exploring the specific roles and mechanisms of different MSC-exos in wound healing, as well as their limitations and potential applications. Understanding the biological properties of MSC-exos is crucial for developing cell-free therapies for wound healing and cutaneous regeneration.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Oncology
Ganesan Ramamoorthi, Krithika Kodumudi, Corey Gallen, Nadia Nocera Zachariah, Amrita Basu, Gabriella Albert, Amber Beyer, Colin Snyder, Doris Wiener, Ricardo L. B. Costa, Brian J. Czerniecki
Summary: Metastatic spread in breast cancer patients is the main cause of cancer-related deaths. Understanding the biological mechanisms of breast cancer cell dissemination, dormancy, and reactivation is important. This review discusses the molecular pathways involved in breast cancer cell dissemination, the role of chemokine-chemokine receptor networks in DCCs migration, DCCs phenotypic heterogeneity, and unique gene signatures in tumor dormancy.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Enrique Alfaro, Pablo Lopez-Jimenez, Jose Gonzalez-Martinez, Marcos Malumbres, Jose A. Suja, Rocio Gomez
Summary: The study reveals that during meiotic divisions in male mice, centrosomes duplicate twice to form bipolar spindles, with Polo-like kinase 1 playing a central role in centrosome assembly, maturation, migration, and spindle formation during spermatogenesis. Inhibition of both Polo-like kinase 1 and Aurora A in organotypic cultures of seminiferous tubules highlights their prominent role in regulating the formation of meiotic bipolar spindles.
Article
Biochemistry & Molecular Biology
Antonio Galarreta, Pablo Valledor, Patricia Ubieto-Capella, Vanesa Lafarga, Eduardo Zarzuela, Javier Munoz, Marcos Malumbres, Emilio Lecona, Oscar Fernandez-Capetillo
Summary: Inhibitors of USP7 lead to widespread activation of CDK1 throughout the cell cycle, causing DNA damage and toxicity to mammalian cells. Additionally, USP7 interacts with the phosphatase PP2A, facilitating its active localization in the cytoplasm, and inhibition of USP7 or PP2A results in similar changes in the phosphoproteome, including increased phosphorylation of CDK1 targets.
Article
Medicine, Research & Experimental
Jose Gonzalez-Martinez, Andrzej W. Cwetsch, Diego Martinez-Alonso, Luis R. Lopez-Sainz, Jorge Almagro, Anna Melati, Jesus Gomez, Manuel Perez-Martinez, Diego Megias, Jasminka Boskovic, Javier Gilabert-Juan, Osvaldo Grana-Castro, Alessandra Pierani, Axel Behrens, Sagrario Ortega, Marcos Malumbres
Summary: The study reveals that defects in certain genes during development can lead to mild MCPH symptoms, while the lack of centrosome or centriole regulators can cause chromosomal instability in neural progenitor cells.
Article
Medicine, Research & Experimental
Sonia Solanes-Casado, Arancha Cebrian, Maria Rodriguez-Remirez, Ignacio Mahillo, Laura Garcia-Garcia, Anxo Rio-Vilarino, Natalia Banos, Guillermo de Carcer, Ana Monfort-Vengut, Victor Castellano, Maria Jesus Fernandez-Acenero, Jesus Garcia-Foncillas, Laura del Puerto-Nevado
Summary: New therapeutic targets have transformed the clinical management of colorectal cancer, with PLK1 inhibitors showing promise but facing challenges of drug resistance. In vitro generation and analysis of resistant cell lines revealed mechanisms such as AXL pathway activation and EMT, with simvastatin and drug combinations proving effective in resensitizing resistant cells. Targeting the mevalonate pathway emerges as a new strategy for overcoming PLK1 inhibitor resistance.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Jose Gonzalez-Martinez, Andrzej W. Cwetsch, Javier Gilabert-Juan, Jesus Gomez, Guillermo Garaulet, Paulina Schneider, Guillermo de Carcer, Francisca Mulero, Eduardo Caleiras, Diego Megias, Eva Porlan, Marcos Malumbres
Summary: This study reveals that the centrosomal kinase PLK1 regulates centrosome asymmetry and cell fate in neural progenitors. Loss of PLK1 activity leads to reduced asymmetry and increased expansion of neural progenitors, promoting cortical growth. However, deficiencies in MCPH proteins result in increased centrosome asymmetry and microcephaly.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Oncology
Donna M. Edwards, Dana K. Mitchell, Zahi Abdul-Sater, Ka-Kui Chan, Zejin Sun, Aditya Sheth, Ying He, Li Jiang, Jin Yuan, Richa Sharma, Magdalena Czader, Pei-Ju Chin, Yie Liu, Guillermo de Carcer, Grzegorz Nalepa, Hal E. Broxmeyer, D. Wade Clapp, Elizabeth A. Sierra Potchanant
Summary: The study highlights the importance of mitotic regulation in the development of malignancies associated with the FA pathway deficiency. By introducing heterozygosity of the spindle assembly checkpoint regulator Mad2 in Fancc-/- mice, researchers were able to create a mouse model that better replicates the high risk of myeloid malignancies seen in FA patients. This suggests that error-prone cell division may play a key role in cancer development in FA patients.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Alberto Martin, Carolina Epifano, Borja Vilaplana-Marti, Ivan Hernandez, Rocio I. R. Macias, Angel Martinez-Ramirez, Ana Cerezo, Pablo Cabezas-Sainz, Maria Garranzo-Asensio, Sandra Amarilla-Quintana, Deborah Gomez-Dominguez, Eduardo Caleiras, Jordi Camps, Gonzalo Gomez-Lopez, Marta Gomez de Cedron, Ana Ramirez de Molina, Rodrigo Barderas, Laura Sanchez, Susana Velasco-Miguel, Ignacio Perez de Castro
Summary: Despite being frequently observed in cancer cells, chromosomal instability (CIN) and aneuploidy have adverse effects on cellular homeostasis. Epitranscriptomic marks catalyzed by RNA-modifying enzymes change under stress, but their association with aneuploidy is still unknown. TRMT61B, a mitochondrial RNA methyltransferase enzyme, is found to be associated with high levels of aneuploidy in cancer cells. Depletion of TRMT61B induces senescence in cells with low aneuploidy, and apoptosis in cells with high aneuploidy. These findings suggest TRMT61B as a potential biomarker for targeting highly aneuploid tumors.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Cell Biology
Ines Berenguer, Pablo Lopez-Jimenez, Irene Mena, Alberto Viera, Jesus Page, Jose Gonzalez-Martinez, Carolina Maestre, Marcos Malumbres, Jose A. Suja, Rocio Gomez
Summary: The haspin-H3T3ph-chromosomal passenger complex (CPC) pathway is crucial for the regulation of centromeres during mammalian male meiosis, controlling chromosome segregation and spindle attachment. This study provides new insights into the functions of haspin kinase and the H3T3ph histone mark in meiotic centromere regulation.
JOURNAL OF CELL SCIENCE
(2022)
Review
Pharmacology & Pharmacy
Ana Monfort-Vengut, Guillermo de Carcer
Summary: Rigosertib is a small-molecule compound currently in phase III clinical trials for the treatment of various myelodysplastic syndromes and leukemias. However, its clinical progress has been hindered by a lack of understanding of its mechanism of action.
Review
Cell Biology
Natalia Sanz-Gomez, Maria Gonzalez-Alvarez, Javier De Las Rivas, Guillermo de Carcer
Summary: Chromosome instability is a well-recognized characteristic of cancer, resulting in increased genetic variability of tumor cells, which facilitates cancer aggressiveness and poor prognosis. Whole-Genome Duplication (WGD) and subsequent polyploidy are main causes of chromosomal instability. Recent studies have revealed that WGD occurs in the early stages of cell transformation, enabling cells to later become aneuploid and drive cancer progression. However, other research suggests that polyploidy acts as a tumor suppressor by inducing cell cycle arrest, cell senescence, apoptosis, and cell differentiation, depending on the tissue type. There is still a knowledge gap regarding how cells undergoing WGD can overcome its deleterious effects and evolve into tumoral cells. Some laboratories in the field of chromosomal instability have recently explored this paradox and identified biomarkers that modulate polyploid cells to become oncogenic. This review provides a historical perspective on how WGD and polyploidy impact cell fitness and cancer progression and summarizes the latest studies describing genes that help cells adapt to polyploidy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Oncology
Jesus Garcia-Donas, Alicia Hurtado, Laia Garrigos, Ana Santaballa, Andres Redondo, Laura Vidal, Nuria Lainez, Eva Guerra, Victor Rodriguez, Juan Cueva, Isabel Bover, Isabel Palacio, Maria Jesus Rubio, Mario Prieto, Jose Antonio Lopez-Guerrero, Juan Francisco Rodriguez-Moreno, Zaida Garcia-Casado, Elena Garcia-Martinez, Alvaro Taus, Ignacio Perez de Castro, Paloma Navarro, Enrique Grande
Summary: Digoxin can inhibit the growth of gastrointestinal tumor cells and induce apoptosis, indicating its potential anti-tumor effect.
CLINICAL & TRANSLATIONAL ONCOLOGY
(2023)
Meeting Abstract
Biotechnology & Applied Microbiology
C. Epifano, D. Gomez-Dominguez, B. Vilaplana-Marti, I. Hernandez, M. Sena-Esteves, I. Perez de Castro
HUMAN GENE THERAPY
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Sara Perez-Luz, Gema Gomez-Mariano, Ignacio Perez de Castro, Iago Justo, Alberto Marcacuzco, Loreto Hierro, Cristina Garfia, Beatriz Martinez-Delgado
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Meeting Abstract
Biotechnology & Applied Microbiology
D. Gomez-Dominguez, S. Amarilla, C. Epifano, A. Martin, B. Vilaplana-Marti, I. Hernandez, M. Pallares, I. Perez de Castro
HUMAN GENE THERAPY
(2021)