Titre
Oncogenic ALK <sup>F1174L</sup> drives tumorigenesis in cutaneous squamous cell carcinoma.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Gualandi, M.
Auteure/Auteur
Iorio, M.
Auteure/Auteur
Engeler, O.
Auteure/Auteur
Serra-Roma, A.
Auteure/Auteur
Gasparre, G.
Auteure/Auteur
Schulte, J.H.
Auteure/Auteur
Hohl, D.
Auteure/Auteur
Shakhova, O.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
2575-1077
Statut éditorial
Publié
Date de publication
2020-06
Volume
3
Numéro
6
Première page
e201900601
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Résumé
Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer characterized by increased mortality. Here, we show for the first time that anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase of the insulin receptor superfamily, plays a pivotal role in the pathogenesis of cSCC. Our data demonstrate that the overexpression of the constitutively active, mutated ALK, ALK <sup>F1174L</sup> , is sufficient to initiate the development of cSCC and is 100% penetrant. Moreover, we show that cSCC development upon ALK <sup>F1174L</sup> overexpression is independent of the cell-of-origin. Molecularly, our data demonstrate that ALK <sup>F1174L</sup> cooperates with oncogenic Kras <sup>G12D</sup> and loss of p53, well-established events in the biology of cSCC. This cooperation results in a more aggressive cSCC type associated with a higher grade histological morphology. Finally, we demonstrate that Stat3 is a key downstream effector of ALK <sup>F1174L</sup> and likely plays a role in ALK <sup>F1174L</sup> -driven cSCC tumorigenesis. In sum, these findings reveal that ALK can exert its tumorigenic potential via cooperation with multiple pathways crucial in the pathogenesis of cSCC. Finally, we show that human cSCCs contain mutations in the ALK gene. Taken together, our data identify ALK as a new key player in the pathogenesis of cSCC, and this knowledge suggests that oncogenic ALK signaling can be a target for future clinical trials.
Sujets
PID Serval
serval:BIB_3430322C06A8
PMID
Open Access
Oui
Date de création
2020-04-25T16:51:51.679Z
Date de création dans IRIS
2025-05-20T17:54:52Z
Fichier(s)![Vignette d'image]()
En cours de chargement...
Nom
32312912_BIB_3430322C06A8.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
3.24 MB
Format
Adobe PDF
PID Serval
serval:BIB_3430322C06A8.P001
URN
urn:nbn:ch:serval-BIB_3430322C06A81
Somme de contrôle
(MD5):ad04126a88bdba2e4bea7e203b8ccbe3