Article
Biochemistry & Molecular Biology
Maria Chiara Gelmi, Robert M. Verdijk, Laurien E. Houtzagers, Pieter A. van der Velden, Wilma G. M. Kroes, Gregorius P. M. Luyten, T. H. Khanh Vu, Martine J. Jager
Summary: MITF is an important regulator of melanogenesis and melanocyte development. MITF loss in uveal melanoma is associated with a shift in epithelial-to-mesenchymal transition factors and increased inflammation. Low MITF expression is also related to genetic changes such as monosomy 3/BAP1 loss and 8q gain/amplification.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Plant Sciences
Danni Feng, Zhongxiang Fang, Pangzhen Zhang
Summary: This article summarizes the melanin inhibitory properties of plant extracts and phytochemicals. The study found that some plant extracts and chemicals can inhibit melanin production through different mechanisms. However, most of the research results were only proven in cellular and animal models, and only a few substances were proven effective in human trials. Further research is needed to develop natural and safe skin whitening products.
Article
Oncology
Malak Sabbah, Mohammad Krayem, Ahmad Najem, Francois Sales, Wilson Miller, Sonia del Rincon, Ahmad Awada, Ghanem E. Ghanem, Fabrice Journe
Summary: The study demonstrated that dasatinib sensitivity is limited to melanoma cell lines with c-Kit alterations, but unexpectedly showed lower efficacy at higher concentrations commonly found in patient blood. By activating the CRTC3/MITF/Bcl-2 pathway, dasatinib may explain the weak clinical benefit in melanoma patients, independently of commonly associated MAPK and PI3K/AKT pathway reactivation.
MOLECULAR CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Yonghua Hu, Yuan Zhou, Xiaohua Hu, Qiaoling Chen, Yan Shi, Jiangxing Zhuang, Qin Wang
Summary: Cefotaxime sodium (CTX) was found to inhibit melanin synthesis by influencing the expression of various proteins related to melanogenesis. Additionally, CTX can regulate intracellular signaling pathways to inhibit melanin production. Furthermore, CTX has been shown to inhibit body pigmentation in zebrafish.
PROCESS BIOCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Jie Liu, Hongtao Nie, Zhongming Huo, Xiwu Yan
Summary: Studies have shown that shellfish have an innate immune system, which plays a crucial role in their disease resistance. Microphthalmia-associated transcription factor (MITF), as a transcription factor, is involved in the regulation of the immune response and shell color is an important breeding index for R. philippinarum. Understanding the immune response mechanism of RPMITFs can provide valuable data for breeding excellent clam varieties. In this study, RpMITF genes were selected as the target gene family, with 12 members and varying lengths and amino acid compositions. Real-time quantitative PCR revealed significant expression of the RpMITF gene family in the hepatopancreas tissues of clam populations after V. anguillarum stress.
BIOCHEMICAL GENETICS
(2023)
Article
Multidisciplinary Sciences
Michael Hamm, Pierre Sohier, Valerie Petit, Jeremy H. Raymond, Veronique Delmas, Madeleine Le Coz, Franck Gesbert, Colin Kenny, Zackie Aktary, Marie Pouteaux, Florian Rambow, Alain Sarasin, Nisamanee Charoenchon, Alfonso Bellacosa, Luis Sanchez-del-Campo, Laura Mosteo, Martin Lauss, Dies Meijer, Eirikur Steingrimsson, Goran B. Jonsson, Robert A. Cornell, Irwin Davidson, Colin R. Goding, Lionel Larue
Summary: BRN2 is a key transcription factor that regulates melanoma invasion, but its role in melanoma initiation was previously unclear. This study shows that BRN2 acts as a haplo-insufficient tumor suppressor that positively regulates PTEN expression, and in the context of BRAF mutation and heterozygous PTEN, loss of BRN2 promotes melanoma initiation and progression.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Miles C. Andrews, Junna Oba, Chang-Jiun Wu, Haifeng Zhu, Tatiana Karpinets, Caitlin A. Creasy, Marie-Andree Forget, Xiaoxing Yu, Xingzhi Song, Xizeng Mao, A. Gordon Robertson, Gabriele Romano, Peng Li, Elizabeth M. Burton, Yiling Lu, Robert Szczepaniak Sloane, Khalida M. Wani, Kunal Rai, Alexander J. Lazar, Lauren E. Haydu, Matias A. Bustos, Jianjun Shen, Yueping Chen, Margaret B. Morgan, Jennifer A. Wargo, Lawrence N. Kwong, Cara L. Haymaker, Elizabeth A. Grimm, Patrick Hwu, Dave S. B. Hoon, Jianhua Zhang, Jeffrey E. Gershenwald, Michael A. Davies, P. Andrew Futreal, Chantale Bernatchez, Scott E. Woodman
Summary: The regulation of distinct intrinsic phenotypic states in melanoma involves complex molecular mechanisms, which are associated with immune features within tumors and have differential correlations with immunotherapy efficacy. These findings have significant implications for cancer biology and the development of new therapeutic strategies.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Jose L. Sanchez-Gloria, Roxana Carbo, Mabel Buelna-Chontal, Horacio Osorio-Alonso, Adrian Henandez-Diazcouder, Rosa Luz de la Fuente-leon, Julio Sandoval, Fausto Sanchez, I. Rubio-Gayosso, Fausto Sanchez-Munoz
Summary: Chronic cold exposure exacerbates MCT-induced pulmonary arterial hypertension in rats, resulting in increased levels of inflammatory markers and miRNAs in plasma EVs and lungs.
Article
Multidisciplinary Sciences
Carolyn R. Maskin, Renuka Raman, Yariv Houvras
Summary: Researchers have identified PPP6C as a key regulator of MITF, a lineage specific transcription factor in melanocytes and an oncogene in melanoma. Inactivation of PPP6C increases MITF expression and target gene expression, decreases sensitivity to BRAF inhibition, and may serve as a potential drug target for melanoma.
SCIENTIFIC REPORTS
(2022)
Article
Medicine, Research & Experimental
Yuqiu Wang, Tianbi Duan, Minhua Hong, Yanting Zhou, Hui Huang, Xiao Xiao, Jing Zheng, Hu Zhou, Zhi Lu
Summary: The study revealed that silk fibroin inhibits melanin synthesis in B16 melanoma cells by down-regulating MITF and tyrosinase expression, suggesting a potential application of silk fibroin in the future.
Article
Oncology
Dimosthenis Michelakis, Konstantinos Lasithiotakis, Ippokratis Messaritakis, Christos Ioannou, Kostas Perisynakis, Ioannis Souglakos, Dimitrios Stamatiou, Gregory Chlouverakis, Eelco de Bree, Ioannis Romanos, Odysseas Zoras
Summary: TM-HILP is associated with increased levels of CMCs, but this increase is not related to patient survival. Patients who experience a complete response to TM-HILP demonstrate higher levels of MITF shortly after the operation.
INTERNATIONAL JOURNAL OF HYPERTHERMIA
(2021)
Article
Biochemistry & Molecular Biology
Chaoyi Li, Qian Chen, Junjiao Wu, Jie Ren, Mengfei Zhang, Huakun Wang, Jinchen Li, Yu Tang
Summary: This study identified two novel compound heterozygous TYR variants in a Chinese patient with hypopigmentation. The variants were found to cause impaired or complete loss of function of TYR, and one variant showed potential therapeutic benefits through gene editing. This study expands the understanding of TYR variants in OCA1 and can facilitate genetic counseling and clinical diagnosis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Sun Young Moon, Kazi-Marjahan Akter, Mi-Jeong Ahn, Kwang Dong Kim, Jiyun Yoo, Joon-Hee Lee, Jeong-Hyung Lee, Cheol Hwangbo
Summary: Researchers have found that fraxinol, a natural coumarin derived from Fraxinus plants, can effectively stimulate melanogenesis, which may have potential value in the treatment of chronic depigmentation conditions such as vitiligo.
Article
Biochemistry & Molecular Biology
Alexander Swoboda, Robert Soukup, Oliver Eckel, Katharina Kinslechner, Bettina Wingelhofer, David Schoerghofer, Christina Sternberg, Ha T. T. Pham, Maria Vallianou, Jaqueline Horvath, Dagmar Stoiber, Lukas Kenner, Lionel Larue, Valeria Poli, Friedrich Beermann, Takashi Yokota, Stefan Kubicek, Thomas Krausgruber, Andre F. Rendeiro, Christoph Bock, Rainer Zenz, Boris Kovacic, Fritz Aberger, Markus Hengstschlaeger, Peter Petzelbauer, Mario Mikula, Richard Moriggl
Summary: The study found that STAT3 can promote the metastatic process of melanoma and antagonize MITF through direct induction of CEBP family member transcription, thereby playing different roles in melanoma progression.
Article
Cell Biology
Zaizhou Liu, Kaige Chen, Jun Dai, Peng Xu, Wei Sun, Wanlin Liu, Zhixin Zhao, Steven P. Bennett, Peifeng Li, Tiancheng Ma, Yuqi Lin, Akinori Kawakami, Jing Yu, Fei Wang, Chunxi Wang, Miao Li, Peter Chase, Peter Hodder, Timothy P. Spicer, Louis Scampavia, Chunyang Cao, Lifeng Pan, Jiajia Dong, Yong Chen, Biao Yu, Min Guo, Pengfei Fang, David E. Fisher, Jing Wang
Summary: The researchers discovered that the structure of MITF is hyperdynamic and vulnerable to dimer-disrupting mutations. They also identified a small molecule compound, TT-012, that specifically binds to MITF and inhibits its transcriptional activity in melanoma cells. Furthermore, TT-012 inhibits the growth of high-MITF melanoma cells and suppresses tumor growth and metastasis in animal models. This study provides insights into the unique dimer interface of the melanoma oncoprotein MITF and presents a potential therapeutic approach to suppress MITF activity.
Article
Multidisciplinary Sciences
Mylene Tajan, Marc Hennequart, Eric C. Cheung, Fabio Zani, Andreas K. Hock, Nathalie Legrave, Oliver D. K. Maddocks, Rachel A. Ridgway, Dimitris Athineos, Alejandro Suarez-Bonnet, Robert L. Ludwig, Laura Novellasdemunt, Nikolaos Angelis, Vivian S. W. Li, Georgios Vlachogiannis, Nicola Valeri, Nello Mainolfi, Vipin Suri, Adam Friedman, Mark Manfredi, Karen Blyth, Owen J. Sansom, Karen H. Vousden
Summary: The study demonstrates that inhibition of PHGDH in the serine synthesis pathway, in conjunction with serine and glycine depletion, can inhibit one-carbon metabolism and cancer growth to enhance therapeutic efficacy. This treatment shows effectiveness against drug-resistant tumors in mice, although there are differences in the ATF4 response between in vitro and in vivo settings.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Hiroshi Kondo, Colin D. H. Ratcliffe, Steven Hooper, James Ellis, James MacRae, Marc Hennequart, Christopher W. Dunsby, Kurt Anderson, Erik Sahai
Summary: The study tracks the transition and heritability of metabolic states in single PIK3CA mutant breast cancer cells, identifying non-genetic glycolytic heterogeneity. It reveals distinct subpopulations of cells with regulated glycolytic and mitochondrial metabolism by PI3K signaling, bromodomain activity, and cell crowding effects, showing how targeting these pathways affects specific subpopulations of cancer cells.
Article
Genetics & Heredity
Eva Morava, Ulrich A. Schatz, Pernille M. Torring, Mary-Alice Abbott, Matthias Baumann, Charlotte Brasch-Andersen, Nathalie Chevalier, Ulrike Dunkhase-Heinl, Martin Fleger, Tobias B. Haack, Stephen Nelson, Sven Potelle, Silvia Radenkovic, Guido T. Bommer, Emile Van Schaftingen, Maria Veiga-da-Cunha
Summary: Deficiency of PGM2L1 leads to a genetic syndrome with severe developmental and speech delay, dysmorphic facial features, ear anomalies, and other symptoms. The syndrome does not appear to be a glycosylation defect, but suggests an unknown role of glucose-1,6-bisphosphate or other sugar bisphosphates in brain metabolism.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Editorial Material
Immunology
Stefania Cane, Vincenzo Bronte
Summary: In the colonic environment, sustained Wnt-beta-catenin activation in regulatory T cells leads to epigenetic rewiring towards proinflammatory ROR gamma t(+) T-reg cells, whose expansion correlates with the progression from inflammatory bowel disease (IBD) to colorectal cancer (CRC).
Review
Immunology
Julianna Blagih, Marc Hennequart, Fabio Zani
Summary: Regulatory T cells play a crucial role in mitigating inflammation and their function is influenced by nutrients. Mitochondrial oxidative metabolism is essential for Treg differentiation and adaptability. Tregs demonstrate different adaptability in various tissue environments, such as their ability to survive in tumor tissues.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Isaac P. Heremans, Francesco Caligiore, Isabelle Gerin, Marina Bury, Marilena Lutz, Julie Graff, Vincent Stroobant, Didier Vertommen, Aurelio A. Teleman, Emile Van Schaftingen, Guido T. Bommer
Summary: This study reveals that PARK7, an enzyme mutated in hereditary Parkinson's disease, plays a protective role against damage caused by a metabolite of glycolysis. The findings provide important insights into the link between metabolism and the development of Parkinson's disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Marc Hennequart, Christiaan F. Labuschagne, Mylene Tajan, Steven E. Pilley, Eric C. Cheung, Nathalie M. Legrave, Paul C. Driscoll, Karen H. Vousden
Summary: Cancer cells grown under physiological metabolite levels show decreased sensitivity to serine withdrawal. Limiting serine availability leads to increased de novo serine synthesis and utilization of hypoxanthine to support purine synthesis. This study enhances our understanding of serine metabolism under physiologically relevant nutrient conditions and suggests potential interventions for enhancing therapeutic response to dietary serine/glycine limitation.
NATURE COMMUNICATIONS
(2021)
Meeting Abstract
Biochemistry & Molecular Biology
Isaac P. Heremans, Francesco Caligiore, Isabelle Gerin, Marina Bury, Marilena Lutz, Julie Graff, Vincent Stroobant, Didier Vertommen, Aurelio Teleman, Emile Van Schaftingen, Guido T. Bommer
Article
Immunology
Federica Calzetti, Giulia Finotti, Nicola Tamassia, Francisco Bianchetto-Aguilera, Monica Castellucci, Stefania Cane, Silvia Lonardi, Chiara Cavallini, Alessandro Matte, Sara Gasperini, Ilaria Signoretto, Fabio Benedetti, Massimiliano Bonifacio, William Vermi, Stefano Ugel, Vincenzo Bronte, Cristina Tecchio, Patrizia Scapini, Marco A. Cassatella
Summary: Cassatella and colleagues have identified the earliest neutrophil-committed progenitor cells in the human bone marrow. These cells share similar characteristics with mature neutrophil subsets expressing interferon-stimulated genes in diseased individuals. This discovery sheds light on the early stages of neutrophil development and is of significant importance.
Article
Biochemistry & Molecular Biology
Manuel Johanns, Cyril Corbet, Roxane Jacobs, Melissa Drappier, Guido T. Bommer, Gaetan Herinckx, Didier Vertommen, Nicolas Tajeddine, David Young, Joris Messens, Olivier Feron, Gregory R. Steinberg, Louis Hue, Mark H. Rider
Summary: Pharmacological activation of AMPK is an attractive approach for the treatment of type 2 diabetes. This study investigated the effects of 991 and other direct AMPK activators on hepatic glucose production and found that 991 can inhibit gluconeogenesis independent of AMPK activity. The inhibition of glucose production by 991 may be explained by the inhibition of mitochondrial pyruvate uptake and inhibition of mitochondrial sn-glycerol-3-phosphate dehydrogenase-2.
BIOCHEMICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Francesco Caligiore, Erika Zangelmi, Carola Vetro, Takfarinas Kentache, Joseph P. Dewulf, Maria Veiga-da-Cunha, Emile Van Schaftingen, Guido Bommer, Alessio Peracchi
Summary: Transaminases can react with alternative substrates, although with low efficiency, and are ineffective at utilizing sugars and sugar derivatives, except for dihydroxyacetone phosphate.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Multidisciplinary Sciences
Joseph P. Dewulf, Manon Martin, Sandrine Marie, Fabie Oguz, Leila Belkhir, Julien De Greef, Jean Cyr Yombi, Xavier Wittebole, Pierre-Francois Laterre, Michel Jadoul, Laurent Gatto, Guido T. Bommer, Johann Morelle
Summary: In this study, quantitative urine metabolomics analysis revealed significant increases in tryptophan metabolites in the urine of COVID-19 patients, which were associated with disease severity and systemic inflammation.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Fabio Zani, Julianna Blagih, Tim Gruber, Michael D. Buck, Nicholas Jones, Marc Hennequart, Clare L. Newell, Steven E. Pilley, Pablo Soro-Barrio, Gavin Kelly, Nathalie M. Legrave, Eric C. Cheung, Ian S. Gilmore, Alex P. Gould, Cristina Garcia-Caceres, Karen H. Vousden
Summary: Artificial sweeteners, calorie-free substitutes for sugar, are widely used in many food products. However, concerns have been raised about the long-term safety of consuming certain sweeteners. This study shows that high doses of sucralose can have immunomodulatory effects, limiting T cell proliferation and differentiation, affecting membrane order, T cell receptor signaling, and intracellular calcium mobilization. Mice given sucralose showed decreased T cell responses in cancer and bacterial infection models, as well as reduced T cell function in autoimmune models. These findings suggest that sucralose intake can dampen T cell-mediated responses, which may be useful in treating T cell-dependent autoimmune disorders.
Article
Cell Biology
Stefania Cane, Roza Maria Barouni, Marina Fabbi, John Cuozzo, Giulio Fracasso, Annalisa Adamo, Stefano Ugel, Rosalinda Trovato, Francesco De Sanctis, Mauro Giacca, Rita Lawlor, Aldo Scarpa, Borislav Rusev, Gabriella Lionetto, Salvatore Paiella, Roberto Salvia, Claudio Bassi, Susanna Mandruzzato, Silvano Ferrini, Vincenzo Bronte
Summary: Preclinical studies have shown that myeloid cells can suppress antitumor immunity by degrading L-arginine, but differences in ARG1 expression and function in rodents and humans have hindered clinical translation. This study discovered that neutrophil extracellular traps (NETs) released by activated neutrophils in patients with PDAC create a microdomain where cathepsin S (CTSS) cleaves human ARG1 (hARG1) into different forms with enhanced enzymatic activity. These NET-associated hARG1 molecules suppress T lymphocytes, but their proliferation can be restored by blocking CTSS cleavage or using hARG1-specific monoclonal antibodies, suggesting potential therapeutic strategies for PDAC.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Steven E. Pilley, Marc Hennequart, Anke Vandekeere, Julianna Blagih, Nathalie M. Legrave, Sarah-Maria Fendt, Karen H. Vousden, Christiaan F. Labuschagne
Summary: Detached cancer cells accumulate and secrete proline, potentially promoting tumor progression by increasing extracellular matrix production and providing proline to surrounding cells.