Review
Biochemistry & Molecular Biology
Mai K. L. Nguyen, Jaimy Jose, Mohamed Wahba, Marc Bernaus-Esque, Andrew J. Hoy, Carlos Enrich, Carles Rentero, Thomas Grewal
Summary: Cancer cells undergo metabolic adaptions to meet their increased bioenergetic needs, including an increased demand for cholesterol. They uptake cholesterol from low-density lipoproteins (LDL) and distribute it from late endosomes/lysosomes (LE/Lys) to other organelles to promote cancer growth and spread. Understanding the regulation of cholesterol transporters and related proteins in LE/Lys is important for developing treatment strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Xinyi Ren, Xiaopu Guo, Zihan Liang, Renxian Guo, Shaohui Liang, Han Liu
Summary: Cell migration is a complex process that involves the coordination of various cellular components. In this study, we discovered a novel interaction between IQGAP1 and Hax1, which plays a significant role in focal adhesion turnover and directional cell migration. Our findings suggest that Hax1 acts as a link between dynamic focal adhesions and IQGAP1, facilitating efficient cell migration. Perturbation of the IQGAP1/Hax1 interaction impairs focal adhesion turnover and inhibits directional cell migration.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Cell Biology
Stephen D. Williams, Tunde M. Smith, LaMonica Stewart, Amos M. Sakwe
Summary: Hypoxia in the tumor microenvironment affects the expression of Annexin A6 (AnxA6) in triple-negative breast cancer cells and their response to targeted therapies. Downregulation of AnxA6 inhibits resistance to EGFR and AR inhibitors, suggesting that targeting AnxA6 could be beneficial in overcoming drug resistance.
Article
Oncology
Thi My Hang Nguyen, Yi-Shyun Lai, Ying-Chi Chen, Tzu-Chien Lin, Ngoc Thang Nguyen, Wen-Tai Chiu
Summary: This study found that under hypoxic conditions, the transcription factor YAP is activated in mesenchymal triple-negative breast cancer (TNBC) cells, promoting cell migration. In addition, hypoxia causes the accumulation of focal adhesions (FAs) at the leading edge of tumor cells. However, the use of the YAP inhibitor verteporfin significantly reduces cell migration and prevents the accumulation of FAs under hypoxic conditions, but only in mesenchymal TNBC cells.
Article
Cell Biology
Ioanna Antoniades, Maria Kyriakou, Anna Charalambous, Katerina Kalalidou, Andri Christodoulou, Maria Christoforou, Paris A. Skourides
Summary: The study successfully prevented the action of FAK at focal adhesions by generating a specific peptide structure, thereby effectively inhibiting the migration and invasion of tumor cells and providing a new direction for the development of anti-metastatic agents.
CELL COMMUNICATION AND SIGNALING
(2021)
Article
Cell Biology
Lisa Dobson, William B. Barrell, Zahra Seraj, Steven Lynham, Sheng-Yuan Wu, Matthias Krause, Karen J. Liu
Summary: This study demonstrates that murine neural crest cells display actin-based lamellipodia and filopodia in vivo. Serine-threonine kinase GSK3 and cytoskeletal regulator Lpd are found to be required for lamellipodia formation while preventing focal adhesion maturation. These findings improve the understanding of cytoskeletal regulation in mammalian neural crest migration and have implications for neural crest anomalies and cancer.
Article
Biology
Karin Legerstee, Jason Sueters, Tsion E. Abraham, Johan A. Slotman, Gert-Jan Kremers, Jacob P. Hoogenboom, Adriaan B. Houtsmuller
Summary: Focal adhesions (FAs) are important cellular structures that connect the intracellular cytoskeleton to the extracellular matrix. This study used a combination of fluorescence and scanning electron microscopy (SEM) to examine FAs and their associated actin fibres. The results revealed the presence of a highly abundant, novel fork structure at the FA-actin interface in a majority of FAs.
Article
Pharmacology & Pharmacy
Baran E. Gueler, Joshua Linnert, Uwe Wolfrum
Summary: VLGR1/ADGRV1 is a large adhesion G protein-coupled receptor associated with Usher syndrome, epilepsy, and other diseases. It is expressed widely in the CNS, eye, and inner ear. Previous research has shown that VLGR1 plays a role in focal adhesion dynamics and cell migration. This study aimed to elucidate the mechanisms of VLGR1 in focal adhesion turnover.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Multidisciplinary Sciences
Jason A. Estep, Lu O. Sun, Martin M. Riccomagno
Summary: Integrin Adhesion Complexes (IACs) act as links between the cytoskeleton and extracellular environment, participating in cellular motility, tissue morphogenesis, anchorage-dependent growth, and cell survival. Focal Adhesion Kinase (FAK) is a critical organizer of IAC signaling events and a genetic and therapeutic target. This study presents the design and characterization of reversible Bimolecular Complementation sensors to monitor FAK phosphorylation in living cells, providing novel means to quantify IAC signaling.
Article
Peripheral Vascular Disease
Dian Liu, Mingjun Zhang, Jingjing Tian, Mingxiao Gao, Ming Liu, Xiangrui Fu, Tao Jin, Jinyu Pan, Fangna Chen, Fengshuang An
Summary: In this study, it was found that WISP1 enhances the stability of atherosclerotic plaques by inhibiting VSMC apoptosis and promoting VSMC migration and proliferation. The underlying mechanisms mainly involve the PI3K/Akt/mTOR, integrin alpha 5 beta 1, and FAK/MEK/ERK signaling pathways.
JOURNAL OF HYPERTENSION
(2022)
Article
Medicine, Research & Experimental
Virginia Actis Dato, Aleyda Benitez-Amaro, Eduardo Garcia, Lene Claudi, Maria Teresa LaChica Lhoest, Antoni Iborra, Jose Maria Guerra, Joan Carles Escola-Gil, Valerie Samouillan, Carlos Enrich, Gustavo Chiabrando, Vicenta Llorente-Cortes
Summary: The study found that targeting the P3 sequence on LRP1 through anti-P3 antibodies can specifically reduce CE accumulation in the heart and restore InsR and GLUT4 levels in the hearts of rabbits fed with a high-fat diet.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Gastroenterology & Hepatology
Carlos Sanz-Garcia, Yulia A. Nevzorova, Eduardo Martinez-Naves, Francisco Javier Cuberoa
Summary: There is a lack of understanding in the pathophysiology of chronic liver disease due to the absence of experimental models that can accurately mimic the human disease. Moreover, the diagnosis of the disease in its early stages is challenging because of the lack of biomarkers. Therefore, the formation of a multidisciplinary consortium from different countries with a direct translation is crucial.
GASTROENTEROLOGIA Y HEPATOLOGIA
(2023)
Article
Biochemistry & Molecular Biology
Nuria Bielsa, Mireia Casasampere, Jose Luis Abad, Carlos Enrich, Antonio Delgado, Gemma Fabrias, Jose M. Lizcano, Josefina Casas
Summary: This study investigates the mechanism of cytotoxicity induced by the natural sphingolipid Jaspine B in lung adenocarcinoma cells. The findings suggest that Jaspine B can induce cytoplasmic vacuolation and methuosis, and that the activation of AMPK may be involved.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Lake-Ee Quek, Michelle van Geldermalsen, Yi Fang Guan, Kanu Wahi, Chelsea Mayoh, Seher Balaban, Angel Pang, Qian Wang, Mark J. Cowley, Kristin K. Brown, Nigel Turner, Andrew J. Hoy, Jeff Holst
Summary: This study reveals that glutamine-indispensable triple-negative breast cancer (TNBC) cells rely on a non-canonical glutamine-to-glutamate overflow, which increases TCA cycle fluxes and replenishes TCA cycle intermediates. The coupling of glucose and glutamine catabolism hampers TNBC cells' ability to oxidize glucose when glutamine is limiting.
Article
Oncology
Blossom Mak, Hui-Ming Lin, Thy Duong, Kate L. Mahon, Anthony M. Joshua, Martin R. Stockler, Howard Gurney, Francis Parnis, Alison Zhang, Tahlia Scheinberg, Gary Wittert, Lisa M. Butler, David Sullivan, Andrew J. Hoy, Peter J. Meikle, Lisa G. Horvath
Summary: This study found that simvastatin can modify the poor lipid profile in men with metastatic castration-resistant prostate cancer (mCRPC). Higher levels of sphingolipids, which are associated with poor prognosis, were reduced after simvastatin treatment. These findings are important for improving overall survival and therapeutic outcomes in mCRPC patients.
Article
Oncology
Diandra Zipinotti dos Santos, Isabella dos Santos Guimaraes, Mariam F. Hakeem-Sanni, Blake J. Cochran, Kerry-Anne Rye, Thomas Grewal, Andrew J. Hoy, Leticia B. A. Rangel
Summary: This study investigates the role of cholesterol metabolism in breast cancer cell response to cisplatin (CDDP) treatment. The findings suggest that altered cholesterol homeostasis contributes to chemotherapy resistance, and co-administration of CDDP and ATV can effectively reduce cell proliferation and viability. The study also identifies ACAT-1 expression as a potential target for overcoming CDDP resistance.
Review
Hematology
Bradley Tucker, James Ephraums, Thomas W. King, Kaivalya Abburi, Kerry-Anne Rye, Blake J. Cochran
Summary: Atherosclerosis is a complex chronic disease characterized by cholesterol accumulation and vascular inflammation. The link between inflammation and cholesterol in atherosclerosis is not fully understood. Myeloid cells, such as monocytes, macrophages, and neutrophils, play critical roles in the disease. While the role of macrophages in cholesterol accumulation and inflammation is well-known, the interaction between cholesterol and neutrophils remains poorly defined.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Chemistry, Medicinal
Valerie Samouillan, Eduardo Garcia, Aleyda Benitez-Amaro, Maria Teresa La Chica Lhoest, Jany Dandurand, Virginia Actis Dato, Jose Maria Guerra, Joan Carles Escola-Gil, Gustavo Chiabrando, Carlos Enrich, Vicenta Llorente-Cortes
Summary: The accumulation of lipids in cardiomyocytes leads to cardiac dysfunction. Blocking cardiomyocyte cholesteryl ester (CE) loading specifically with antibodies against the P3 sequence of the LRP1 receptor improves cardiac insulin sensitivity. The impact of anti-P3 antibodies on biophysical alterations was analyzed.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Cardiac & Cardiovascular Systems
Richard Ying Ke Zhang, Blake J. Cochran, Shane R. Thomas, Kerry-Anne Rye
Summary: Excessive inflammation and impaired healing after myocardial infarction (MI) can lead to heart failure. The repair process of MI can be divided into three phases: the inflammatory phase, the proliferative phase, and the maturation phase, each with distinct functions and consequences. Macrophages, neutrophils, and lymphocytes play important roles in these phases, but their functions across each phase are not well characterized. Immunomodulatory therapies targeting inflammation have not been successful in large clinical trials, possibly due to a lack of understanding of temporal changes in immune cell functions. Improved understanding of immune cell function over time is crucial for developing effective treatments for preventing heart failure after MI.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Geriatrics & Gerontology
Judith Canto-Santos, Laura Valls-Roca, Ester Tobias, Francesc Josep Garcia-Garcia, Mariona Guitart-Mampel, Anna Esteve-Codina, Beatriz Martin-Mur, Mercedes Casado, Rafael Artuch, Estel Solsona-Vilarrasa, Jose Carlos Fernandez-Checa, Carmen Garcia-Ruiz, Carles Rentero, Carlos Enrich, Pedro J. J. Moreno-Lozano, Jose Cesar Milisenda, Francesc Cardellach, Josep M. M. Grau-Junyent, Gloria Garrabou
Summary: In this study, molecular disturbances were found in fibroblast samples from IBM patients, including abnormal gene expression related to inflammation, mitochondria, and cell cycle regulation, as well as functional changes in inflammatory, autophagy, mitochondrial, and metabolic processes. These findings contribute to a better understanding of the pathogenesis of IBM and provide insights for the identification of new biomarkers and therapeutic strategies.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2023)
Article
Multidisciplinary Sciences
Jordan F. Hastings, Sharissa L. Latham, Alvin Kamili, Madeleine S. Wheatley, Jeremy Z. R. Han, Marie Wong-Erasmus, Monica Phimmachanh, Max Nobis, Chiara Pantarelli, Antonia L. Cadell, Yolande E. I. O'Donnell, King Ho Leong, Sophie Lynn, Fan-Suo Geng, Lujing Cui, Sabrina Yan, Joanna Achinger-Kawecka, Clare Stirzaker, Murray D. Norris, Michelle Haber, Toby N. Trahair, Frank Speleman, Katleen De Preter, Mark J. Cowley, Ozren Bogdanovic, Paul Timpson, Thomas R. Cox, Walter Kolch, Jamie I. Fletcher, Dirk Fey, David R. Croucher
Summary: Gene expression noise promotes stochastic drug resistance in rare cancer cells. However, when integrated across multiple components of an apoptotic signaling network, the influence of noise leads to a higher frequency of chemoresistant neuroblastoma cells. These cells are characterized by JNK impairment and retain a memory of their resistant state even after chemotherapy treatment.
Review
Hematology
Thomas W. King, Blake J. Cochran, Kerry-Anne Rye
Summary: ApoA-I, the main component of HDL, has multiple cardioprotective and antidiabetic functions. This review summarizes the current knowledge of apoA-I's antidiabetic effects, the mechanism behind these effects, and the potential of small peptides that mimic apoA-I to be used as innovative treatments for diabetes.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Raquel Fucho, Estel Solsona-Vilarrasa, Sandra Torres, Susana Nunez, Naroa Insausti-Urkia, Albert Edo, Maria Calvo, Anna Bosch, Gemma Martin, Carlos Enrich, Carmen Garcia-Ruiz, Jose C. Fernandez-Checa
Summary: In this study, we found that StARD1 is predominantly expressed in the perivenous zone of the liver in patients with chronic alcoholic liver disease. This zonal-dependent expression of StARD1 results in the accumulation of cholesterol and increased lipid peroxidation in mitochondria, leading to liver cell injury. We also observed changes in mitochondrial morphology and function following alcohol intake. These findings highlight the importance of StARD1 in the pathogenesis of alcoholic liver disease.
JOURNAL OF LIPID RESEARCH
(2023)
Article
Medicine, Research & Experimental
Shiqi Zhong, Raphael Chevre, David Castano Mayan, Maria Corliano, Blake J. Cochran, Kai Ping Sem, Theo H. van Dijk, Jianhe Peng, Liang Juin Tan, Siddesh V. Hartimath, Boominathan Ramasamy, Peter Cheng, Albert K. Groen, Folkert Kuipers, Julian L. Goggi, Chester Drum, Rob M. van Dam, Ru San Tan, Kerry-Anne Rye, Michael R. Hayden, Ching-Yu Cheng, Shaji Chacko, Jason Flannick, Xueling Sim, Hong Chang Tan, Roshni R. Singaraja
Summary: Reduced CYP8B1 activity is associated with increased insulin sensitivity in humans, possibly due to increased skeletal muscle insulin sensitivity caused by increased circulating CDCA.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
