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JOURNAL ARTICLE
Federico Mauri, Cédric Blanpain
Merkel cell carcinoma (MCC) is a rare but very aggressive neuroendocrine cancer of the skin, with very limited therapeutic options. Although immunotherapy is effective in some cases, there is an unmet need for new therapeutic approaches in MCCs. In this issue of EMBO Molecular Medicine, Leiendecker et al identify a selective vulnerability of MCC for inhibitors of the lysine-specific histone demethylase 1A (LSD1). LSD1 inhibitors promote differentiation of tumor cells toward normal Merkel cell fate, impairing tumor cell growth in vivo, and opening new avenues for the treatment of patients with MCC...
November 6, 2020: EMBO Molecular Medicine
#2
COMMENT
Pauline Vieugué, Cédric Blanpain
In this issue of Developmental Cell, Li et al. develop a novel lineage tracing system to record EMT activity during lung metastasis of mammary tumors. Using EMT-tracer mouse models, they reveal that N-cadherin is transiently expressed by most metastasis-initiating cells and demonstrate its functional importance during the metastatic cascade.
September 14, 2020: Developmental Cell
#3
JOURNAL ARTICLE
Alessia Centonze, Shuheng Lin, Elisavet Tika, Alejandro Sifrim, Marco Fioramonti, Milan Malfait, Yura Song, Aline Wuidart, Jens Van Herck, Anne Dannau, Gaelle Bouvencourt, Christine Dubois, Nina Dedoncker, Amar Sahay, Viviane de Maertelaer, Christian W Siebel, Alexandra Van Keymeulen, Thierry Voet, Cédric Blanpain
Glandular epithelia, including the mammary and prostate glands, are composed of basal cells (BCs) and luminal cells (LCs)1,2 . Many glandular epithelia develop from multipotent basal stem cells (BSCs) that are replaced in adult life by distinct pools of unipotent stem cells1,3-8 . However, adult unipotent BSCs can reactivate multipotency under regenerative conditions and upon oncogene expression3,9-13 . This suggests that an active mechanism restricts BSC multipotency under normal physiological conditions, although the nature of this mechanism is unknown...
August 2020: Nature
#4
JOURNAL ARTICLE
Mariaceleste Aragona, Alejandro Sifrim, Milan Malfait, Yura Song, Jens Van Herck, Sophie Dekoninck, Souhir Gargouri, Gaëlle Lapouge, Benjamin Swedlund, Christine Dubois, Pieter Baatsen, Katlijn Vints, Seungmin Han, Fadel Tissir, Thierry Voet, Benjamin D Simons, Cédric Blanpain
The ability of the skin to grow in response to stretching has been exploited in reconstructive surgery1 . Although the response of epidermal cells to stretching has been studied in vitro2,3 , it remains unclear how mechanical forces affect their behaviour in vivo. Here we develop a mouse model in which the consequences of stretching on skin epidermis can be studied at single-cell resolution. Using a multidisciplinary approach that combines clonal analysis with quantitative modelling and single-cell RNA sequencing, we show that stretching induces skin expansion by creating a transient bias in the renewal activity of epidermal stem cells, while a second subpopulation of basal progenitors remains committed to differentiation...
July 29, 2020: Nature
#5
REVIEW
Jing Yang, Parker Antin, Geert Berx, Cédric Blanpain, Thomas Brabletz, Marianne Bronner, Kyra Campbell, Amparo Cano, Jordi Casanova, Gerhard Christofori, Shoukat Dedhar, Rik Derynck, Heide L Ford, Jonas Fuxe, Antonio García de Herreros, Gregory J Goodall, Anna-Katerina Hadjantonakis, Ruby Y J Huang, Chaya Kalcheim, Raghu Kalluri, Yibin Kang, Yeesim Khew-Goodall, Herbert Levine, Jinsong Liu, Gregory D Longmore, Sendurai A Mani, Joan Massagué, Roberto Mayor, David McClay, Keith E Mostov, Donald F Newgreen, M Angela Nieto, Alain Puisieux, Raymond Runyan, Pierre Savagner, Ben Stanger, Marc P Stemmler, Yoshiko Takahashi, Masatoshi Takeichi, Eric Theveneau, Jean Paul Thiery, Erik W Thompson, Robert A Weinberg, Elizabeth D Williams, Jianhua Xing, Binhua P Zhou, Guojun Sheng
Epithelial-mesenchymal transition (EMT) encompasses dynamic changes in cellular organization from epithelial to mesenchymal phenotypes, which leads to functional changes in cell migration and invasion. EMT occurs in a diverse range of physiological and pathological conditions and is driven by a conserved set of inducing signals, transcriptional regulators and downstream effectors. With over 5,700 publications indexed by Web of Science in 2019 alone, research on EMT is expanding rapidly. This growing interest warrants the need for a consensus among researchers when referring to and undertaking research on EMT...
June 2020: Nature Reviews. Molecular Cell Biology
#6
JOURNAL ARTICLE
Louis Godin, Cédric Balsat, Yves-Rémi Van Eycke, Justine Allard, Claire Royer, Myriam Remmelink, Ievgenia Pastushenko, Nicky D'Haene, Cédric Blanpain, Isabelle Salmon, Sandrine Rorive, Christine Decaestecker
In cancer biology, epithelial-to-mesenchymal transition (EMT) is associated with tumorigenesis, stemness, invasion, metastasis, and resistance to therapy. Evidence of co-expression of epithelial and mesenchymal markers suggests that EMT should be a stepwise process with distinct intermediate states rather than a binary switch. In the present study, we propose a morphological approach that enables the detection and quantification of cancer cells with hybrid E/M states, i.e., which combine partially epithelial (E) and partially mesenchymal (M) states...
April 8, 2020: Cancers
#7
JOURNAL ARTICLE
Sophie Dekoninck, Edouard Hannezo, Alejandro Sifrim, Yekaterina A Miroshnikova, Mariaceleste Aragona, Milan Malfait, Souhir Gargouri, Charlotte de Neunheuser, Christine Dubois, Thierry Voet, Sara A Wickström, Benjamin D Simons, Cédric Blanpain
During embryonic and postnatal development, organs and tissues grow steadily to achieve their final size at the end of puberty. However, little is known about the cellular dynamics that mediate postnatal growth. By combining in vivo clonal lineage tracing, proliferation kinetics, single-cell transcriptomics, and in vitro micro-pattern experiments, we resolved the cellular dynamics taking place during postnatal skin epidermis expansion. Our data revealed that harmonious growth is engineered by a single population of developmental progenitors presenting a fixed fate imbalance of self-renewing divisions with an ever-decreasing proliferation rate...
April 30, 2020: Cell
#8
JOURNAL ARTICLE
Farida Benhadou, Elisabeth Glitzner, Audrey Brisebarre, Benjamin Swedlund, Yura Song, Christine Dubois, Milena Rozzi, Catherine Paulissen, Veronique Del Marmol, Maria Sibilia, Cédric Blanpain
Psoriasis is a common chronic skin disorder characterized by keratinocyte hyperproliferation with altered differentiation accompanied by inflammation and increased angiogenesis. It remains unclear whether the first events that initiate psoriasis development occur in keratinocytes or inflammatory cells. Here, using different psoriasis mouse models, we showed that conditional deletion of Flt1 or Nrp1 in epidermal cells inhibited psoriasis mediated by Vegfa overexpression or c-Jun/JunB deletion. Administration of anti-Nrp1 antibody reverted the psoriasis phenotype...
January 2020: Science Advances
#9
Caterina Miro, Emery Di Cicco, Raffaele Ambrosio, Giuseppina Mancino, Daniela Di Girolamo, Annunziata Gaetana Cicatiello, Serena Sagliocchi, Annarita Nappi, Maria Angela De Stefano, Cristina Luongo, Dario Antonini, Feliciano Visconte, Silvia Varricchio, Gennaro Ilardi, Luigi Del Vecchio, Stefania Staibano, Anita Boelen, Cedric Blanpain, Caterina Missero, Domenico Salvatore, Monica Dentice
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
January 8, 2020: Nature Communications
#10
JOURNAL ARTICLE
Caterina Miro, Emery Di Cicco, Raffaele Ambrosio, Giuseppina Mancino, Daniela Di Girolamo, Annunziata Gaetana Cicatiello, Serena Sagliocchi, Annarita Nappi, Maria Angela De Stefano, Cristina Luongo, Dario Antonini, Feliciano Visconte, Silvia Varricchio, Gennaro Ilardi, Luigi Del Vecchio, Stefania Staibano, Anita Boelen, Cedric Blanpain, Caterina Missero, Domenico Salvatore, Monica Dentice
Epithelial tumor progression often involves epithelial-mesenchymal transition (EMT). We report that increased intracellular levels of thyroid hormone (TH) promote the EMT and malignant evolution of squamous cell carcinoma (SCC) cells. TH induces the EMT by transcriptionally up-regulating ZEB-1, mesenchymal genes and metalloproteases and suppresses E-cadherin expression. Accordingly, in human SCC, elevated D2 (the T3-producing enzyme) correlates with tumor grade and is associated with an increased risk of postsurgical relapse and shorter disease-free survival...
November 27, 2019: Nature Communications
#11
JOURNAL ARTICLE
Tatiana Revenco, Adeline Nicodème, Ievgenia Pastushenko, Magdalena K Sznurkowska, Mathilde Latil, Panagiota A Sotiropoulou, Christine Dubois, Virginie Moers, Sophie Lemaire, Viviane de Maertelaer, Cédric Blanpain
Epithelial-to-mesenchymal transition (EMT) has been proposed to be important for metastatic dissemination. However, recent studies have challenged the requirement of EMT for metastasis. Here, we assessed in different models of primary skin squamous cell carcinomas (SCCs) whether EMT is associated with metastasis. The incidence of metastasis was much higher in SCCs presenting EMT compared to SCCs without EMT, supporting the notion that a certain degree of EMT is required to initiate the metastatic cascade in primary skin SCCs...
November 5, 2019: Cell Reports
#12
JOURNAL ARTICLE
Elisavet Tika, Marielle Ousset, Anne Dannau, Cédric Blanpain
The prostate is formed by a branched glandular epithelium composed of basal cells (BCs) and luminal cells (LCs). Multipotent and unipotent stem cells (SCs) mediate the initial steps of prostate development whereas BCs and LCs are self-sustained in adult mice by unipotent lineage-restricted SCs. The spatiotemporal regulation of SC fate and the switch from multipotency to unipotency remain poorly characterised. Here, by combining lineage tracing, whole-tissue imaging, clonal analysis and proliferation kinetics, we uncover the cellular dynamics that orchestrate prostate postnatal development in mouse...
October 23, 2019: Development
#13
JOURNAL ARTICLE
Nicole Amberg, Panagiota A Sotiropoulou, Gerwin Heller, Beate M Lichtenberger, Martin Holcmann, Bahar Camurdanoglu, Temenuschka Baykuscheva-Gentscheva, Cedric Blanpain, Maria Sibilia
Epidermal growth factor receptor (EGFR) signaling controls skin development and homeostasis in mice and humans, and its deficiency causes severe skin inflammation, which might affect epidermal stem cell behavior. Here, we describe the inflammation-independent effects of EGFR deficiency during skin morphogenesis and in adult hair follicle stem cells. Expression and alternative splicing analysis of RNA sequencing data from interfollicular epidermis and outer root sheath indicate that EGFR controls genes involved in epidermal differentiation and also in centrosome function, DNA damage, cell cycle, and apoptosis...
April 17, 2019: IScience
#14
REVIEW
Sophie Dekoninck, Cédric Blanpain
Tissue repair is critical for animal survival. The skin epidermis is particularly exposed to injuries, which necessitates rapid repair. The coordinated action of distinct epidermal stem cells recruited from various skin regions together with other cell types, including fibroblasts and immune cells, is required to ensure efficient and harmonious wound healing. A complex crosstalk ensures the activation, migration and plasticity of these cells during tissue repair.
January 2019: Nature Cell Biology
#15
REVIEW
Ievgenia Pastushenko, Cédric Blanpain
Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells acquire mesenchymal features. In cancer, EMT is associated with tumor initiation, invasion, metastasis, and resistance to therapy. Recently, it has been demonstrated that EMT is not a binary process, but occurs through distinct cellular states. Here, we review the recent studies that demonstrate the existence of these different EMT states in cancer and the mechanisms regulating their functions. We discuss the different functional characteristics, such as proliferation, propagation, plasticity, invasion, and metastasis associated with the distinct EMT states...
March 2019: Trends in Cell Biology
#16
REVIEW
Piyush B Gupta, Ievgenia Pastushenko, Adam Skibinski, Cedric Blanpain, Charlotte Kuperwasser
Our traditional understanding of phenotypic plasticity in adult somatic cells comprises dedifferentiation and transdifferentiation in the context of tissue regeneration or wound healing. Although dedifferentiation is central to tissue repair and stemness, this process inherently carries the risk of cancer initiation. Consequently, recent research suggests phenotypic plasticity as a new paradigm for understanding cancer initiation, progression, and resistance to therapy. Here, we discuss how cells acquire plasticity and the role of plasticity in initiating cancer, cancer progression, and metastasis and in developing therapy resistance...
January 3, 2019: Cell Stem Cell
#17
JOURNAL ARTICLE
Adriana Sánchez-Danés, Jean-Christophe Larsimont, Mélanie Liagre, Eva Muñoz-Couselo, Gaëlle Lapouge, Audrey Brisebarre, Christine Dubois, Mariano Suppa, Vijayakumar Sukumaran, Véronique Del Marmol, Josep Tabernero, Cédric Blanpain
Basal cell carcinoma (BCC) is the most frequent cancer in humans and results from constitutive activation of the Hedgehog pathway1 . Several Smoothened inhibitors are used to treat Hedgehog-mediated malignancies, including BCC and medulloblastoma2 . Vismodegib, a Smoothened inhibitor, leads to BCC shrinkage in the majority of patients with BCC3 , but the mechanism by which it mediates BCC regression is unknown. Here we used two genetically engineered mouse models of BCC4 to investigate the mechanisms by which inhibition of Smoothened mediates tumour regression...
October 2018: Nature
#18
Aline Wuidart, Alejandro Sifrim, Marco Fioramonti, Shigeru Matsumura, Audrey Brisebarre, Daniel Brown, Alessia Centonze, Anne Dannau, Christine Dubois, Alexandra Van Keymeulen, Thierry Voet, Cédric Blanpain
In the version of this Article originally published, ref. 52 was incorrectly only attributed to its corresponding author, Fre, S., and an older title was used. The correct citation should have been: Lilja, A. M. et al. Clonal analysis of Notch1-expressing cells reveals the existence of unipotent stem cells that retain long-term plasticity in the embryonic mammary gland. Nat. Cell Biol. https://doi.org/10.1038/s41556-018-0108-1 (2018)'. This has now been amended in all online versions of the Article.
September 2018: Nature Cell Biology
#19
JOURNAL ARTICLE
Maud Debaugnies, Adriana Sánchez-Danés, Sandrine Rorive, Maylis Raphaël, Mélanie Liagre, Marie-Astrid Parent, Audrey Brisebarre, Isabelle Salmon, Cédric Blanpain
YAP and TAZ are key downstream regulators of the Hippo pathway, regulating cell proliferation and differentiation. YAP and TAZ activation has been reported in different cancer types. However, it remains unclear whether they are required for the initiation of major skin malignancies like basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Here, we analyze the expression of YAP and TAZ in these skin cancers and evaluate cancer initiation in knockout mouse models. We show that YAP and TAZ are nuclear and highly expressed in different BCC types in both human and mice...
July 2018: EMBO Reports
#20
REVIEW
Adriana Sánchez-Danés, Cédric Blanpain
Squamous cell carcinomas (SCCs) are among the most prevalent human cancers. SCC comprises a wide range of tumours originated from diverse anatomical locations that share common genetic mutations and expression of squamous differentiation markers. SCCs arise from squamous and non-squamous epithelial tissues. Here, we discuss the different studies in which the cell of origin of SCCs has been uncovered by expressing oncogenes and/or deleting tumour suppressor genes in the different cell lineages that compose these epithelia...
September 2018: Nature Reviews. Cancer
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