Review
Genetics & Heredity
Izabela Baryla, Katarzyna Kosla, Andrzej K. Bednarek
Summary: WWOX is a protein that regulates multiple cellular processes and is associated with various cancers and genetic diseases. It plays an important role in normal bone metabolism and metabolic disorders. Its WW domain is involved in the activity regulation of transcription factors such as HIF1 alpha and RUNX2, and it is associated with glucose and basic energy metabolism disturbances.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Article
Biochemistry & Molecular Biology
Jitka Soukupova, Andrea Malfettone, Esther Bertran, Maria Isabel Hernandez-Alvarez, Irene Penuelas-Haro, Francesco Dituri, Gianluigi Giannelli, Antonio Zorzano, Isabel Fabregat
Summary: EMT induced by TGF-beta in HCC cells reprograms lipid metabolism to facilitate the utilization of FFA and the entry of acetyl-CoA into the TCA cycle, to sustain the elevated requirements of energy linked to this process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Huidong Liu, Ye-Guang Chen
Summary: TGF-beta signaling plays a critical role in metabolism and is closely related to the progression of various diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Physiology
Volodymyr V. V. Balatskyi, Adrian Sowka, Pawel Dobrzyn, Oksana O. O. Piven
Summary: The WNT/beta-catenin pathway plays an important regulatory role in cardiac development and growth. Its activity is low in healthy adult hearts, but even this low activity is essential for maintaining normal heart function. Acute activation of the pathway is considered cardioprotective after infarction, while chronically high activity causes profibrotic and hypertrophic effects in the adult heart.
Article
Developmental Biology
Sarah S. McCarthy, Michele Karolak, Leif Oxburgh
Summary: Expansion of interstitial cells in adult kidney is a hallmark of chronic disease, while their proliferation during fetal development is necessary for organ formation. Inactivation of TGF beta/Smad response in mouse interstitial cell lineage leads to overproliferation of interstitial cells regionally in the kidney medulla. Smad4 loss primarily reduces TGF beta signaling in the interstitium, while increasing Wnt/beta-catenin signaling.
Article
Cell Biology
Hussam Husanie, Muhannad Abu-Remaileh, Kian Maroun, Lina Abu-Tair, Hazem Safadi, Karine Atlan, Talia Golan, Rami I. Aqeilan
Summary: This study reveals the essential role of WWOX in pancreatic cancer development and progression. WWOX physically interacts with activators of the TGF-beta signaling pathway, affecting macrophage infiltration and cancer stemness. Overexpression of WWOX in patient-derived xenografts leads to diminished aggressiveness of the tumor.
CELL DEATH & DISEASE
(2022)
Article
Pharmacology & Pharmacy
Huan Zhou, Xingyu Zhu, Yan Yao, Yue Su, Jing Xie, Minhui Zhu, Cuixia He, Jiaxiang Ding, Yuanyuan Xu, Rongfang Shan, Ying Wang, Xiangdi Zhao, Yuzhou Ding, Bingyan Liu, Zhonghuan Shao, Yuanyuan Liu, Tao Xu, Yunqiu Xie
Summary: This study clarified the molecular mechanism of TMEM88 in regulating lipid synthesis and metabolism cytokine in non-alcoholic fatty liver disease (NAFLD). The findings suggest that TMEM88 plays a role in the progression of NAFLD through the Wnt/β-catenin signaling pathway in AML-12 cells.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Cell Biology
Cheng Shoou Lee, Amanda Choo, Sonia Dayan, Robert Richards, Louise O'Keefe
Summary: The review discusses the identification of the WWOX gene and its contribution to disease, while highlighting the unclear normal biological role of WWOX. Using the genetically tractable model organism Drosophila melanogaster has shed light on the integral role of WWOX in metabolism and raises outstanding questions about the biological relationship between WWOX and the FRA16D common chromosomal fragile site, as well as the substrate and product of the WWOX enzyme activity. Understanding the normal role of WWOX and its relationship to chromosomal fragility may be crucial in understanding how perturbation of these roles results in disease.
Article
Cell Biology
Mustafa Karabicici, Yagmur Azbazdar, Gunes Ozhan, Serif Senturk, Zeynep Firtina Karagonlar, Esra Erdal
Summary: In this study, it was found that regorafenib treatment activated Wnt/beta-catenin signaling only in hepatoblast-like HCC cell lines and induced enrichment of markers associated with hepatic stem/progenitor cells. On the other hand, regorafenib resistant cells demonstrated diminished Wnt/beta-catenin signaling activity and enhanced TGF-beta signaling activity. The inhibition of TGF-beta pathway in combination with regorafenib administration might increase regorafenib-induced cell death in HCC tumors with aberrant activation in the Wnt/beta-catenin pathway.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Zoe K. Price, Noor A. Lokman, Masato Yoshihara, Hiroaki Kajiyama, Martin K. Oehler, Carmela Ricciardelli
Summary: Disabled-2 (DAB2) is a key adaptor protein in clathrin mediated endocytosis, regulating signalling pathways involved in homeostasis, cell positioning, and EMT. It functions as a tumour suppressor and negatively regulates key pathways such as MAPK, Wnt, and TGF-β. However, recent studies suggest a complex role of DAB2 in cancer with pro-tumorigenic effects. It is also a common target of microRNAs and has been implicated in promoting metastasis in the tumour microenvironment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Jinyu Zhang, Samuel Rojas, Sanjay Singh, Phillip R. Musich, Matthew Gutierrez, Zhiqiang Yao, Douglas Thewke, Yong Jiang
Summary: The study demonstrates that TGF-beta activates the endothelial-to-mesenchymal transition in human aortic endothelial cells, dependent on the Wnt signaling pathway. Wnt2 signaling is required for TGF-beta-mediated EndMT, and high levels of Wnt2 protein in atherosclerotic lesions confirm its involvement in atherosclerosis in vivo. This suggests that Wnt2 may contribute to atherosclerotic plaque development and could be a potential therapeutic target for controlling atherosclerosis.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Cell Biology
Elia Escasany, Borja Lanzon, Almudena Garcia-Carrasco, Adriana Izquierdo-Lahuerta, Lucia Torres, Patricia Corrales, Ana Elena Rodriguez Rodriguez, Sergio Luis-Lima, Concepcion Martinez Alvarez, Francisco Javier Ruperez, Manuel Ros, Esteban Porrini, Mikael Ryden, Gema Medina-Gomez
Summary: Renal TGF beta 3 may have antifibrotic and renoprotective properties, opposing or counteracting the activity of TGF beta 1. Tgfb3(+/-) mice exhibit glomerular basement membrane thickening and fibrosis, accompanied by oxidative stress and abnormal mitochondrial function.
DISEASE MODELS & MECHANISMS
(2021)
Article
Microbiology
Jialu Zhang, Guanghui Yang, Xuefei Wang, Yaohong Zhu, Jiufeng Wang
Summary: Porcine deltacoronavirus (PDCoV) is an emerging enteropathogenic coronavirus in pigs that poses a threat to human health. A derivative of cholesterol called 25-hydroxycholesterol (25HC) has been found to exhibit antiviral effects against PDCoV and its mechanism involves interference with cholesterol metabolism and suppression of TGF-beta 1.
MICROBIOLOGY SPECTRUM
(2022)
Article
Oncology
Yan-Long Han, Dan Luo, Kakeng Habaxi, Julaiti Tayierjiang, Wei Zhao, Wei Wang, Wumaierjiang Aikebaier, Li Wang
Summary: In this study, we identified COL5A2 as a prognostic gene for osteosarcoma through bioinformatics analysis, and showed that COL5A2 inhibits invasion and metastasis of osteosarcoma by suppressing the TGF-beta and Wnt/β-Catenin signaling pathways.
FRONTIERS IN ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Yoshifumi Takahata, Hiromasa Hagino, Ayaka Kimura, Mitsuki Urushizaki, Shiori Yamamoto, Kanta Wakamori, Tomohiko Murakami, Kenji Hata, Riko Nishimura
Summary: This review article summarizes the research progress on the functions and regulatory mechanisms of lubricin and growth differentiation factor 5 (Gdf5) in osteoarthritis (OA), as well as their roles in maintaining articular cartilage homeostasis and the development of OA. Molecular targeting of Prg4 and Gdf5 is expected to provide new insights into the etiology, pathogenesis, and potential treatment of OA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Zhenguo Zeng, Weiguo Chen, Alexander Moshensky, Zaid Shakir, Raheel Khan, Laura E. Crotty Alexander, Lorraine B. Ware, C. M. Aldaz, Jeffrey R. Jacobson, Steven M. Dudek, Viswanathan Natarajan, Roberto F. Machado, Sunit Singla
Summary: Chronic cigarette smoking is known to increase risk for ARDS, but the risks associated with chronic e-cigarette use are largely unknown. The WWOX gene is highly susceptible to genotoxic stress from environmental exposures and exposure to nicotine-containing e-cigarette vapor resulted in a decrease in WWOX mRNA levels. The downregulation of WWOX may play a role in the increased risk for ARDS in chronic smokers and potentially in chronic e-cigarette users in the future.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2021)
Article
Oncology
Anne Trinh, Carlos R. Gil Del Alcazar, Sachet A. Shukla, Koei Chin, Young Hwan Chang, Guillaume Thibault, Jennifer Eng, Bojana Jovanovic, C. Marcelo Aldaz, So Yeon Park, Joon Jeong, Catherine Wu, Joe Gray, Kornelia Polyak
Summary: The transition from DCIS to IDC involves genetic correlations despite long latency periods and therapeutic interventions. Immune hot and cold tumors can arise early in DCIS, with different degrees of immune cell mixing between DCIS and IDC. Tumor-specific copy-number aberrations and mutations are associated with differences in immune signaling in IDC, potentially modulating immune function and driving the transition to IDC.
MOLECULAR CANCER RESEARCH
(2021)
Article
Oncology
Fabiana Alejandra Rossi, Juliana Haydee Enrique Steinberg, Ezequiel Hernan Calvo Roitberg, Molishree Umesh Joshi, Ahwan Pandey, Martin Carlos Abba, Beatrice Dufrusine, Simonetta Buglioni, Vincenzo De Laurenzi, Gianluca Sala, Rossano Lattanzio, Joaquin Maximiliano Espinosa, Mario Rossi
Summary: The study identifies USP19 as a potential therapeutic target for breast cancer, with its inhibition reducing cell invasiveness and overexpression increasing invasiveness. The mechanism involves the Wnt co-receptor LRP6, and overexpression of USP19 is a prognostic marker for distant relapse in early breast cancer patients.
Article
Multidisciplinary Sciences
Alejandro J. Cagnoni, Maria Laura Giribaldi, Ada G. Blidner, Anabela M. Cutine, Sabrina G. Gatto, Rosa M. Morales, Mariana Salatino, Martin C. Abba, Diego O. Croci, Karina V. Marino, Gabriel A. Rabinovich
Summary: Colorectal cancer is a common malignancy with limited response to immunotherapy, prompting the need for new biomarkers and therapeutic targets. Gal-1, as an endogenous glycan-binding protein, has been found to influence the activity of CD8(+) regulatory T cells in CRC, suggesting a potential immunotherapeutic approach for this disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Valeria Alejandra Ferretti, Romina Canzoneri, Sabina Palma, Ezequiel Lacunza, Claudio Marcelo Aldaz, Martin Carlos Abba
Summary: Rhomboid pseudoproteases such as RHBDD2 play a role in regulating the activity of target proteins in mammary gland development and breast cancer. Interaction studies showed a physical association between RHBDD2 and WWOX in normal and cancer cells, suggesting a potential involvement in breast epithelial cell proliferation and differentiation. WWOX, as a novel target of RHBDD2, may modulate gene expression in breast cells through the TGF beta/SMAD3 signaling pathway.
Article
Biochemical Research Methods
Genaro Camele, Sebastian Menazzi, Hernan Chanfreau, Agustin Marraco, Waldo Hasperue, Matias D. Butti, Martin C. Abba
Summary: Multiomix is an interactive cloud-based platform that helps biologists identify genetic and epigenetic events associated with the transcriptional modulation of cancer-related genes. Users can analyze data from public functional genomic databases or upload their own datasets. Multiomix provides a range of functions, pipelines, and a graphical user interface for retrieving, aggregating, analyzing, and visualizing different omics data sources.
Article
Genetics & Heredity
Dongju Park, Mehdi Gharghabi, Morgan S. Schrock, Rebecca Plow, Teresa Druck, Charles Yungvirt, C. Marcelo Aldaz, Kay Huebner
Summary: Down regulation of Wwox protein expression occurs in many cancers, contributing to insensitivity to ionizing radiation (IR) and platinum drug treatments. Patients with reduced Wwox expression in their cancer tissue show decreased overall survival following these treatments, in accord with our earlier finding that reduced Wwox protein expression in cancers is associated with changes in choice of DNA double-strand break (DSB) repair pathway.
Article
Biochemistry & Molecular Biology
Dongju Park, Mehdi Gharghabi, Colleen R. Reczek, Rebecca Plow, Charles Yungvirt, C. Marcelo Aldaz, Kay Huebner
Summary: Wwox-deficient cells in both humans and mice exhibit elevated homologous recombination. The binding of human Wwox to Brca1 inhibits its phosphorylation, while the binding of murine Wwox to Brca1 affects the DNA break repair pathway through the activation of related proteins. The restoration of sensitivity to ionizing radiation and platinum drugs in Wwox-deficient cells is crucial for cancer treatment research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Maria Laura Fabre, Romina Canzoneri, Agustina Gurruchaga, Jaeho Lee, Pradeep Tatineni, Hyunsuk Kil, Ezequiel Lacunza, C. Marcelo Aldaz, Martin Carlos Abba
Summary: This study characterizes the phenotypic and molecular effects of MALINC1, a long non-coding RNA (lncRNA) that is upregulated in premalignant ductal carcinoma in-situ lesions. MALINC1 is found to behave as an oncogenic and immune-related lncRNA involved in early-stage breast cancer progression. High expression of MALINC1 is associated with a pro-tumorigenic immune environment and a favorable predicted response to immunotherapy.
Article
Biochemistry & Molecular Biology
Nicolas A. Pinto, Martin C. Abba, Lorena Laporte, Juan M. Perez M. Saez, Ada G. G. Blidner, Nicolas I. Torres, Rosa M. M. Morales, Sabrina G. G. Gatto, Camila A. A. Bach, Florencia Veigas, Hernan J. Garcia Rivello, Peng Song, Jane H. H. Frederiksen, Lene Juel Rasmussen, Francoise Poirier, Diego O. O. Croci, Victoria Sundblad, Gabriel A. A. Rabinovich, Juan P. P. Cerliani
Summary: Non-melanoma skin cancer (NMSC) has increased due to chronic exposure to sunlight, climatic changes, and immunosuppression. Gal-7, a protein expressed in skin tissue, plays a critical role in NMSC development. Overexpression of Gal-7 leads to an increase in the number of papillomas in transgenic mice.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Neurosciences
Tabish Hussain, Kevin Sanchez, Jennifer Crayton, Dhurjhoti Saha, Collene Jeter, Yue Lu, Martin Abba, Ryan Seo, Jeffrey L. Noebels, Laura Fonken, C. Marcelo Aldaz
Summary: WWOX gene loss-of-function (LoF) is associated with neuropathologies causing developmental, epileptic, and ataxic phenotypes. A specific variant of the WWOX gene, p.Pro47Thr, has been linked to a new form of autosomal recessive cerebellar ataxia with epilepsy and intellectual disability. A mutant knock-in mouse model of the Wwox P47T mutation was generated, which mimics the human SCAR12 phenotype. The mice exhibited epilepsy, social and cognitive deficits, poor motor coordination, and signs of progressive cerebellar dysfunction.
PROGRESS IN NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Soledad Iseas, Diego Prost, Sarah Bouchereau, Mariano Golubicki, Juan Robbio, Ana Oviedo, Mariana Coraglio, Mirta Kujaruk, Guillermo Mendez, Marcela Carballido, Enrique Roca, Louis Gros, Vincent De Parades, Nabil Baba-Hamed, Julien Adam, Martin Carlos Abba, Eric Raymond
Summary: This retrospective study analyzed the clinical data of 176 patients with anal squamous cell carcinoma who completed chemoradiotherapy. Complete response was found to be predictive of disease-free survival and overall survival. Other prognostic factors included tumor stage, lymph node metastasis, sex, differentiation status, tumor location, and HIV-HPV coinfection. These results provide important insights for the treatment and prognosis evaluation of anal squamous cell carcinoma.
Article
Oncology
Mariana Cooke, Xuyao Zhang, Suli Zhang, Evgeniy Eruslanov, Priti Lal, Reba E. Daniel, Michael D. Feldman, Martin C. Abba, Marcelo G. Kazanietz
Summary: Aberrant expression of protein kinase C (PKC) isozymes is a hallmark of cancer. The classical/conventional PKCα isozyme has been associated with tumor suppression in most cancer types, but in aggressive prostate cancer cells, high expression of PKCα is required for their mitogenic activity. Mechanistic analysis revealed that PKCα controls gene expression, particularly genes and transcriptional networks associated with cell-cycle progression and E2F transcription factors. Silencing PKCα expression in aggressive prostate cancer cells impairs cell-cycle progression, proliferation, invasion, and tumorigenic activity.
CANCER RESEARCH COMMUNICATIONS
(2022)
Meeting Abstract
Oncology
Seyed Javad Moghaddam, Tabish Hussain, Melody Zarghooni, Walter V. Velasco, Linda Phan, Michelle I. Savage, Jennifer T. Fox, Shizuko Sei, Powel H. Brown, C. Marcelo Aldaz
CANCER PREVENTION RESEARCH
(2022)
Meeting Abstract
Oncology
Seyed Javad Moghaddam, Tabish Hussain, Melody Zarghooni, Walter V. Velasco, Linda Phan, Michelle I. Savage, Jennifer T. Fox, Shizuko Sei, Powel H. Brown, C. Marcelo Aldaz
CANCER PREVENTION RESEARCH
(2022)