Anthony Veltri - Academia.edu (original) (raw)

Papers by Anthony Veltri

Methods in molecular biology, 2024

Stem Cells, Oct 31, 2017

Mammalian skin and its appendages constitute the integumentary system forming a barrier between t... more Mammalian skin and its appendages constitute the integumentary system forming a barrier between the organism and its environment. During development, skin epidermal cells divide rapidly and stratify into a multilayered epithelium, as well as invaginate downward in the underlying mesenchyme to form hair follicles (HFs). In postnatal skin, the interfollicular epidermal (IFE) cells continuously proliferate and differentiate while HFs undergo cycles of regeneration. Epidermal regeneration is fueled by epidermal stem cells (SCs) located in the basal layer of the IFE and the outer layer of the bulge in the HF. Epidermal development and SC behavior are mainly regulated by various extrinsic cues, among which Wnt-dependent signaling pathways play crucial roles. This review not only summarizes the current knowledge of Wnt signaling pathways in the regulation of skin development and governance of SCs during tissue homeostasis, but also discusses the potential crosstalk of Wnt signaling with other pathways involved in these processes. STEM CELLS 2018;36:22-35 SIGNIFICANCE STATEMENT This review article provides a concise overview on the current knowledge of Wnt signaling pathways in the regulation of skin development, hair follicle morphogenesis, and governance of epidermal stem cells during tissue homeostasis. The spatial and temporal interconnections of Wnt/ß-catenin and ß-catenin-independent Wnt signaling in the developmental and homeostatic processes of skin are also highlighted. Using epidermal development and regeneration as examples, this study calls attention to the potential crosstalk between Wnt signaling with other pathways that co-orchestrate these processes.

Cancers, Aug 21, 2019

The skin functions as a barrier between the organism and the surrounding environment. Direct expo... more The skin functions as a barrier between the organism and the surrounding environment. Direct exposure to external stimuli and the accumulation of genetic mutations may lead to abnormal cell growth, irreversible tissue damage and potentially favor skin malignancy. Skin homeostasis is coordinated by an intricate signaling network, and its dysregulation has been implicated in the development of skin cancers. Wnt signaling is one such regulatory pathway orchestrating skin development, homeostasis, and stem cell activation. Aberrant regulation of Wnt signaling cascades not only gives rise to tumor initiation, progression and invasion, but also maintains cancer stem cells which contribute to tumor recurrence. In this review, we summarize recent studies highlighting functional evidence of Wnt-related oncology in keratinocyte carcinomas, as well as discussing preclinical and clinical approaches that target oncogenic Wnt signaling to treat cancers. Our review provides valuable insight into the significance of Wnt signaling for future interventions against keratinocyte carcinomas.

Nature Communications, Aug 1, 2022

Hair follicles undergo cycles of regeneration fueled by hair follicle stem cells (HFSCs). While β... more Hair follicles undergo cycles of regeneration fueled by hair follicle stem cells (HFSCs). While β-catenin-dependent canonical Wnt signaling has been extensively studied and implicated in HFSC activation and fate determination, very little is known about the function of β-catenin-independent Wnt signaling in HFSCs. In this study, we investigate the functional role of ROR2, a Wnt receptor, in HFSCs. By analyzing Ror2-depleted HFSCs, we uncover that ROR2 is not only essential to regulate Wnt-activated signaling that is responsible for HFSC activation and self-renewal, but it is also required to maintain proper ATM/ATR-dependent DNA damage response, which is indispensable for the long-term maintenance of HFSCs. In analyzing HFSCs lacking β-catenin, we identify a compensatory role of ROR2-PKC signaling in protecting β-cateninnull HFSCs from the loss of stem cell pool. Collectively, our study unveils a previously unrecognized role of ROR2 in regulation of stem cell self-renewal and maintenance. In mammals, Wnt signaling functions in tissue morphogenesis, stem cell activation, and tumor development 1,2. The binding of secreted Wnt ligands to receptors and/or co-receptors initiates diverse signaling cascades that can be divided into β-catenin-dependent canonical and β-catenin-independent non-canonical Wnt signaling pathways 1. These pathways might act independently or cooperatively to orchestrate various cellular functions. Canonical Wnt signaling (referred as Wnt/β-catenin signaling) is activated when a Wnt ligand binds to Frizzled (Fzd) and LRP-5/6, which triggers activation of Dishevelled (Dvl) proteins, leading to the inhibition of the destruction complex, composed by Axin, caseine kinase 1α (CK1α), adenomatous polyposis coli (APC) and glycogen synthase kinase 3β (GSK3β), thereby stabilizing β-catenin 3,4. Stabilized β-catenin protein then translocates to the nucleus where it binds to lymphoid-enhancing factor/T-cell factor (LEF/TCF) proteins to activate target gene expression 5. Unlike Wnt/β-catenin signaling, β-catenin-independent Wnt pathways involve multiple intracellular signaling cascades that might be cross-connected. The induction of non-canonical Wnt signaling may trigger the release of intracellular calcium, which in turn activates downstream protein kinases, such as calcium/calmodulin-dependent protein kinase II (CaMKII) and protein kinase C (PKC) 6-8. Non-canonical Wnt signaling can also be transduced via Rho family of the small GTPases, which activate c-Jun N-terminal kinase (JNK) and the downstream activating protein-1 (AP-1) complex for transcriptional regulation, or directly modulate cytoskeleton organization that orchestrates planar cell polarity (PCP) and cell migration 9-13. Receptor tyrosine kinase-like orphan receptor 2 (ROR2) was initially identified along with ROR1 as a tyrosine kinase of the Trk family 14 , and then recognized as one of Wnt (co-)receptors due to its ability to interact with non-canonical Wnts, including Wnt4, Wnt5a, and Wnt11 15,16. Genetic studies show that Ror2 −/− mice displayed striking similarities to Wnt5a −/− mice, suggesting they may function in the same signaling pathway 10,17. In vertebrates, ROR2 is required for Wnt5ainduced cell migration, a function that involves activation of JNK, PKC, actin-binding protein Filamin A and Rho-family of the GTPase 17-21. The interaction of Wnt-ROR2 leads to phosphorylation of Dvl that induces the activation of AP-1 and Rac1 22,23. In addition, ROR2 was shown to interact with and be phosphorylated by CK1and GSK3, both of kinases that also play imperative roles in Wnt/β-catenin signaling 20,24-26. In multiple systems, Wnt5a was shown to inhibit β-catenin-mediated canonical Wnt signaling 27-29. The nature by which ROR2 mediates

« Beaucoup remercier signifie secrètement demander davantage. » Proverbe anglais es premières pen... more « Beaucoup remercier signifie secrètement demander davantage. » Proverbe anglais es premières pensées vont au personnel du laboratoire de Physiologie humaine et Pharmacologie. Tout d'abord, j'aimerais adresser ma plus sincère gratitude au Professeur Bruno Flamion pour m'avoir accueilli dans son laboratoire et pour avoir mis à ma disposition l'infrastructure nécessaire afin de mener à bien ce travail. Par la présente je témoigner de la confiance et des avis judicieux dont il m'a gratifié et lui suis également reconnaissant pour la richesse de nos discussions et la pertinence de ses remarques. Ensuite, je dois beaucoup au Docteur Rachid Seqqat pour avoir partagé ses connaissances et pour n'avoir jamais été avare de son temps. Nul doute que son expérience m'a été d'une aide précieuse. Tous mes remerciements et ma gratitude vont aussi à Martine Albert, Guy Dehousse et Camille Fautré pour avoir mis, avec beaucoup de gentillesse, leur adresse technique à mon service. Enfin, je remercie Bénédicte André, Virginie Bourguignon, Sophie Dogné, Cécile Onclinx, Stéphanie Meunier et Jenifer Defoux pour le plaisir et le privilège que j'ai eu à travailler en leur compagnie. Vous avez indubitablement contribué à l'avancement et à la réussite de mon travail. Que soient également remerciés les membres du jury : Madame Sophie Dogné, le professeur Nathalie Caron, le professeur Martine Raes et Monsieur Julien Lemaire. Je porte une attention particulière à Johanne Dubail, membre du laboratoire de biologie des tissus conjonctifs dirigé par le Docteur Alain Colige (ULg). Merci de m'avoir aidé lors de l'instillation des souris, et ce, dans les meilleures conditions possible. Sur un plan plus personnel, j'exprime une éternelle gratitude à ceux qui ont toujours été à mes côtés, à savoir mes amis, ma famille, et plus particulièrement mes parents. Je tiens aussi à me remercier de m'être engagé vers le chemin de la réussite alors que je n'y étais pas destiné. En dernier lieu, je dédicace ce travail à une personne grâce à laquelle j'ai trouvé ma voie, le Docteur Biondina Mantini. À tous, Ma reconnaissance est grande Et comment pourrait-il en être autrement ? Riche, je le suis d'avoir bénéficié de votre soutien, de votre aide et de votre connaissance Ce que vous avez fait pour moi est cher à mes yeux Infiniment redevable, je vous en remercie.

Cancers, 2019