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
Biochemistry & Molecular Biology
Lenka Kyjacova, Rafael Saup, Kerstin Roensch, Sabine Wallbaum, Stefanie Dukowic-Schulze, Amelia Foss, Sandra D. Scherer, Melanie Rothley, Antje Neeb, Nicole Grau, Wilko Thiele, Sonja Thaler, Natascha Cremers, Carsten Sticht, Norbert Gretz, Boyan K. Garvalov, Jochen Utikal, Jonathan P. Sleeman
Summary: The sustained expression of IER2 drives melanoma invasion and progression through stimulating osteopontin secretion by inducing senescence in melanoma cells. Coordinate expression of IER2, p53/p21, and osteopontin in melanomas and metastases highlights the pathophysiological relevance of IER2-mediated senescence in melanoma progression.
Article
Medicine, Research & Experimental
Letizia Porcelli, Annalisa Mazzotta, Marianna Garofoli, Roberta Di Fonte, Gabriella Guida, Michele Guida, Stefania Tommasi, Amalia Azzariti
Summary: The crosstalk between Notch and MAPK pathway is involved in MEK inhibitor resistance in metastatic melanoma and promotes migration in uveal melanoma cells. The combination of MEK and Notch inhibitors shows synergistic effects in some cells and antagonistic effects in others. In uveal melanoma cells, the combination therapy can block cell migration towards liver cancer cells and induce cells into a senescent-like state.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Zhi Liu, Aleksandar Krstic, Ashish Neve, Cristina Casalou, Nora Rauch, Kieran Wynne, Hilary Cassidy, Amanda McCann, Emma Kavanagh, Brendan McCann, Alfonso Blanco, Jens Rauch, Walter Kolch
Summary: KSR1 plays a critical role in mutant BRAF transformation, and its loss results in impaired cell proliferation and migration, cell cycle abnormalities, cellular senescence, and apoptosis. The study reveals that KSR1 directs ERK to phosphorylate substrates essential for cell survival, and its loss activates p38 MAPK pathway leading to cell cycle aberrations and senescence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Emil Rudolf, Kamil Rudolf
Summary: This study investigates the effects of acute chelation of free intracellular zinc pools in melanoma cells and tissues. The results show that the acute loss of free zinc leads to reduced cell proliferation, cell death, oxidative stress, lysosomal damage, and premature senescence. The responses to zinc loss vary among individual melanoma models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Jiahua Liu, Runzi Zheng, Yanghuan Zhang, Shuting Jia, Yonghan He, Jing Liu
Summary: This review provides an overview of the molecular mechanisms, microenvironmental factors, and therapeutic strategies of skin aging and melanoma, and discusses potential common targets between melanoma and cell senescence.
Article
Cell Biology
Tom Zimmermann, Michaela Pommer, Viola Kluge, Chafia Chiheb, Susanne Muehlich, Anja-Katrin Bosserhoff
Summary: Detection and quantification of senescent cells is challenging. It is accepted to use a combination of markers and cellular characteristics to define senescent cells in vitro. This study provides a comprehensive comparison of biomarkers and cellular characteristics used to detect senescence in melanocytic systems, aiming to support the development of standardized senescence detection and quantification.
Article
Oncology
Alexandra R. R. Esimbekova, Nadezhda V. V. Palkina, Ivan S. S. Zinchenko, Vasiliy D. D. Belenyuk, Andrey A. A. Savchenko, Ekaterina Yu Sergeeva, Tatiana G. Ruksha
Summary: It has been found that the anticancer drug dacarbazine can induce melanoma cells to enter the G(0) phase of the cell cycle, leading to drug resistance. The transition to the G(0) phase is associated with the VEGFA-VEGFR2 signaling pathway and cell cycle signaling. Treatment of melanoma cells with dacarbazine resulted in an increase in G(0)-positive cells. These findings may contribute to a better understanding of the mechanisms of drug resistance in melanoma.
Article
Environmental Sciences
Iulia Pinzaru, Raul Chioibas, Iasmina Marcovici, Dorina Coricovac, Razvan Susan, Denisa Predut, Doina Georgescu, Cristina Dehelean
Summary: Malignant melanoma is the deadliest type of skin cancer with limited treatment options in advanced stages. Herbal constituent rutin (RUT) has shown potential as a chemotherapeutic agent against melanoma due to its antioxidant, antimicrobial, anti-inflammatory, UV-filtering, and SPF-enhancing properties. This study focused on evaluating RUT's cytotoxic potential against two human melanoma cell lines, showing dose-dependent decrease in cell viability and senescence-inducing properties. Further studies are needed to elucidate the mechanisms of RUT-induced cytotoxicity and senescence in melanoma cells despite the in vitro anti-melanoma effect observed.
Article
Oncology
Svenja Meierjohann
Summary: Melanomas and melanocytes are frequently exposed to UV, resulting in DNA damage and reactive oxygen stress related harm. This can lead to multinucleation or polyploidy, with the cells either experiencing mitotic catastrophe and death or surviving and acquiring new features to adapt to stress. This review focuses on polyploidy inducers in melanoma, their effects on transcriptional reprogramming and phenotypic adaptation, and the significance of polyploid melanoma cells in therapy resistance.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Oncology
Abraham L. Bayer, Jodie Pietruska, Jaymes Farrell, Siobhan McRee, Pilar Alcaide, Philip W. Hinds
Summary: Cellular senescence is a critical process regulated by AKT isoforms and NF-kappa B pathway, and plays a role in cancer progression. This study demonstrates that AKT1 is essential for CDK4/6 inhibitor-induced senescence and its effect is independent of cGAS. Targeting AKT1 in combination with CDK4/6 inhibitors could be a potential therapeutic strategy to induce senescence without promoting cancer progression.
Article
Cell Biology
Sizhu Lu, Pakavarin Louphrasitthiphol, Nishit Goradia, Jean-Philippe Lambert, Johannes Schmidt, Jagat Chauhan, Milap G. Rughani, Lionel Larue, Matthias Wilmanns, Colin R. Goding
Summary: Lu et al. investigated the role of TBX2 in melanoma, revealing its association with PI3K signaling and its binding with E2F1 to promote proliferation and bypass senescence. By discovering the interaction between TBX2 and various transcription factors and cofactors, they explored how PI3K signaling modulates the function of TBX2 in cancer.
GENES & DEVELOPMENT
(2021)
Article
Cell Biology
Ping Meng, Jiewu Huang, Xian Ling, Shan Zhou, Jingyan Wei, Mingsheng Zhu, Jinhua Miao, Weiwei Shen, Jiemei Li, Huiyun Ye, Hongxin Niu, Yunfang Zhang, Lili Zhou
Summary: This study reveals the important role of CXCR2 in renal fibrosis, primarily through inducing beta-catenin-activated mitochondrial dysfunction and promoting tubular cell senescence. CXCR2 antagonists and beta-catenin signaling blockers may have therapeutic potential in inhibiting these processes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Jose Mario Gonzalez-Meljem, Juan Pedro Martinez-Barbera
Summary: Cellular senescence can prevent tumour development autonomously but also promote tumour growth non-autonomously by creating a permissive tumour microenvironment. In a specific pituitary tumour ACP, senescent cell clusters with SASP play a critical role in tumour initiation. Evidence suggests that paracrine signalling from senescent cells may underlie tumourigenesis in various tumour and cancer models.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Cell Biology
Liming Tian, Dan Ke, Yi Hong, Chong Zhang, Daizhi Tian, Long Chen, Lirui Zhan, Shiqin Zong
Summary: The semi-synthetic derivative of artemisinin, artesunate, has been shown to alleviate UVB irradiation-induced skin photoaging by suppressing cell senescence, intracellular ROS production, p16(INK4a) expression, and apoptosis, and promoting proliferation and expression of SOD and beta-catenin in HaCaT cells. These results offer novel insights into the pharmacological activity of artesunate.
Article
Medicine, Research & Experimental
Michael Olvedy, Julie C. Tisserand, Flavie Luciani, Bram Boeckx, Jasper Wouters, Sophie Lopez, Florian Rambow, Sara Aibar, Bernard Thienpont, Jasmine Barra, Corinna Kohler, Enrico Radaelli, Sophie Tartare-Deckert, Stein Aerts, Patrice Dubreuil, Joost J. van den Oord, Diether Lambrechts, Paulo De Sepulveda, Jean-Christophe Marine
JOURNAL OF CLINICAL INVESTIGATION
(2017)
Article
Oncology
Caroline Bonet, Flavie Luciani, Jean-Francois Ottavi, Justine Leclerc, Fanelie-Marie Jouenne, Marina Boncompagni, Karine Bille, Veronique Hofman, Guillaume Bossis, Gian Marco de Donatis, Thomas Strub, Yann Cheli, Mickael Ohanna, Frederic Luciano, Sandrine Marchetti, Stephane Rocchi, Marie-Christine Birling, Marie-Francoise Avril, Nicolas Poulalhon, Thomas Luc, Paul Hofman, Jean-Philippe Lacour, Irwin Davidson, Brigitte Bressac-de Paillerets, Robert Ballotti, Jean-Christophe Marine, Corine Bertolotto
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2017)
Article
Oncology
Pierre Sohier, Lea Legrand, Zackie Aktary, Christine Grill, Veronique Delmas, Florence Bernex, Edouard Reyes-Gomez, Lionel Larue, Beatrice Vergier
PIGMENT CELL & MELANOMA RESEARCH
(2018)
Article
Cell Biology
Francesca Zalfa, Vincenzo Panasiti, Simone Carotti, Maria Zingariello, Giuseppe Perrone, Laura Sancillo, Laura Pacini, Flavie Luciani, Vincenzo Roberti, Silvia D'Amico, Rosa Coppola, Simona Osella Abate, Rosa Alba Rana, Anastasia De Luca, Mark Fiers, Valentina Melocchi, Fabrizio Bianchi, Maria Giulia Farace, Tilmann Achsel, Jean-Christophe Marine, Sergio Morini, Claudia Bagni
CELL DEATH & DISEASE
(2017)
Letter
Dermatology
C. Grill, L. Benzekri, A. Rubod, Z. Aktary, K. Ezzedine, A. Taieb, Y. Gauthier, L. Larue, V. Delmas
BRITISH JOURNAL OF DERMATOLOGY
(2018)
Article
Oncology
Elise Bonvin, Enrico Radaelli, Martin Bizet, Flavie Luciani, Emilie Calonne, Pascale Putmans, David Nittner, Nitesh Kumar Singh, Sara Francesca Santagostino, Valerie Petit, Lionel Larue, Jean Christophe Marine, Francois Fuks
Review
Dermatology
Veronique Delmas, Lionel Larue
EXPERIMENTAL DERMATOLOGY
(2019)
Article
Oncology
Valerie Petit, Jeremy Raymond, Christophe Alberti, Marie Pouteaux, Stuart J. Gallagher, Mai Q. Nguyen, Andrew E. Aplin, Veronique Delmas, Lionel Larue
PIGMENT CELL & MELANOMA RESEARCH
(2019)
Article
Multidisciplinary Sciences
Anca G. Radu, Sakina Torch, Florence Fauvelle, Karin Pernet-Gallay, Anthony Lucas, Renaud Blervaque, Veronique Delmas, Uwe Schlattner, Laurence Lafanechere, Pierre Hainaut, Nicolas Tricaud, Veronique Pingault, Nadege Bondurand, Nabeel Bardeesy, Lionel Larue, Chantal Thibert, Marc Bilaud
Article
Oncology
Hussein Akil, Mercedes Quintana, Jeremy H. Raymond, Tommy Billoux, Valentin Benboubker, Sophie Besse, Philippe Auzeloux, Veronique Delmas, Valerie Petit, Lionel Larue, Michel D'Incan, Francoise Degoul, Jacques Rouanet
Summary: Targeted radionuclide therapy (TRT) combined with MAPK/ERK inhibitors shows additive efficiency in BRAF and NRAS mutant melanoma cells. TRT has a significant therapeutic effect on NRAS(Q61K) mutated melanoma and reduces metastasis capacity.
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
Developmental Biology
Sophie Colombo, Valerie Petit, Roselyne Y. Wagner, Delphine Champeval, Ichiro Yajima, Franck Gesbert, Zackie Aktary, Irwin Davidson, Veronique Delmas, Lionel Larue
Summary: This study found that overexpression of β-catenin promotes differentiation of Schwann cell precursors (SCPs) towards the melanocyte lineage within a specific temporal window. Additionally, excessive activation of β-catenin also leads to marked hyperpigmentation in the paws.
Article
Dermatology
Ikrame Lazar, Emily Clement, Lorry Carrie, David Esteve, Stephanie Dauvillier, Mohamed Moutahir, Stephane Dalle, Veronique Delmas, Nathalie Andrieu-Abadie, Lionel Larue, Catherine Muller, Laurence Nieto
Summary: Obesity is associated with the occurrence and development of melanoma. The mechanism involves the downregulation of p16(INK4A) expression in melanoma cells by adipocytes through beta-catenin-dependent regulation, which increases cell motility. Adipocytes from individuals with obesity secrete a larger number of vesicles, delivering more beta-catenin to melanoma cells.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Review
Oncology
Jeremy H. Raymond, Zackie Aktary, Lionel Larue, Veronique Delmas
Summary: GPCRs play essential roles in melanogenesis and melanomagenesis, modulating critical cellular processes such as proliferation and migration through cellular signaling. Exploring the new functions of GPCRs is crucial for understanding the mechanisms of melanomagenesis and developing novel therapeutic approaches. Recent advances in the study of GPCRs will undoubtedly expand treatment options for melanoma in the future.
Article
Dermatology
Zackie Aktary, Jeremy H. Raymond, Marie Pouteaux, Veronique Delmas, Valerie Petit, Lionel Larue
Summary: The establishment of consistent genetically modified mouse melanoma models and cell lines is crucial for prevention and treatment. This study reviews different mouse melanoma cell lines and explores the changes they undergo through molecular characterization and modification of the genome and microenvironment. These cell lines with defined genetic mutations enable the testing of innovative therapies and have relevance to human disease.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
