Sökning: onr:"swepub:oai:DiVA.org:liu-179150" >
Trop-2 induces ADAM...
-
Guerra, EmanuelaG dAnnunzio Univ Chieti Pescara, Italy; G dAnnunzio Univ Chieti Pescara, Italy
(författare)
Trop-2 induces ADAM10-mediated cleavage of E-cadherin and drives EMT-less metastasis in colon cancer
- Artikel/kapitelEngelska2021
Förlag, utgivningsår, omfång ...
-
Elsevier Science INC,2021
-
electronicrdacarrier
Nummerbeteckningar
-
LIBRIS-ID:oai:DiVA.org:liu-179150
-
https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-179150URI
-
https://doi.org/10.1016/j.neo.2021.07.002DOI
Kompletterande språkuppgifter
-
Språk:engelska
-
Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
-
Ämneskategori:ref swepub-contenttype
-
Ämneskategori:art swepub-publicationtype
Anmärkningar
-
Funding Agencies|grants of Fondazione of the Cassa di Risparmio della Provincia di Chieti; Compagnia di San PaoloCompagnia di San Paolo [2489IT]; Italian Ministry of Development [MI01_00424]; Region Abruzzo (POR FESR) [C78C14000100005]; Oncoxx Biotech (Italian Ministry of University and Research, Smart Cities and Communities) [SCN_00558]; Programma Per Giovani Ricercatori "Rita Levi Montalcini", Italian Ministry of University and Research [PGR12I7N1Z]
-
We recently reported that activation of Trop-2 through its cleavage at R87-T88 by ADAMIO underlies Trop-2-driven progression of colon cancer. However, the mechanism of action and pathological impact of Trop-2 in metastatic diffusion remain unexplored. Through searches for molecular determinants of cancer metastasis, we identified TROP2 as unique in its up-regulation across independent colon cancer metastasis models. Overexpression of wild-type Trop-2 in KM12SM human colon cancer cells increased liver metastasis rates in vivo in immunosuppressed mice. Metastatic growth was further enhanced by a tail-less, activated Delta cytoTrop-2 mutant, indicating the Trop-2 tail as a pivotal inhibitory signaling element. In primary tumors and metastases, transcriptome analysis showed no down-regulation of CDH1 by transcription factors for epithelial-to-mesenchymal transition, thus suggesting that the pro-metastatic activity of Trop-2 is through alternative mechanisms. Trop-2 can tightly interact with ADAM10. Here, Trop-2 bound E-cadherin and stimulated ADAM10-mediated proteolytic cleavage of E-cadherin intracellular domain. This induced detachment of E-cadherin from beta-actin, and loss of cell-cell adhesion, acquisition of invasive capability, and membrane-driven activation of beta-catenin signaling, which were further enhanced by the Delta cytoTrop-2 mutant. This Trop-2/E-cadherin/beta-catenin program led to anti-apoptotic signaling, increased cell migration, and enhanced cancer-cell survival. In patients with colon cancer, activation of this Trop-2-centered program led to significantly reduced relapse-free and overall survival, indicating a major impact on progression to metastatic disease. Recently, the anti-Trop-2 mAb Sacituzumab govitecan-hziy was shown to be active against metastatic breast cancer. Our findings define the key relevance of Trop-2 as a target in metastatic colon cancer.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
-
Trerotola, MarcoG dAnnunzio Univ Chieti Pescara, Italy; G dAnnunzio Univ Chieti Pescara, Italy
(författare)
-
Relli, ValeriaG dAnnunzio Univ Chieti Pescara, Italy; Oncoxx Biotech, Italy
(författare)
-
Lattanzio, RossanoG dAnnunzio Univ Chieti Pescara, Italy; G dAnnunzio Univ Chieti Pescara, Italy
(författare)
-
Tripaldi, RominaG dAnnunzio Univ Chieti Pescara, Italy
(författare)
-
Vacca, GiovannaG dAnnunzio Univ Chieti Pescara, Italy
(författare)
-
Ceci, MartinaG dAnnunzio Univ Chieti Pescara, Italy
(författare)
-
Boujnah, KhouloudUniv Messina, Italy
(författare)
-
Garbo, ValeriaUniv Messina, Italy
(författare)
-
Moschella, AntoninoUniv Messina, Italy
(författare)
-
Zappacosta, RominaG dAnnunzio Univ Chieti Pescara, Italy
(författare)
-
Simeone, PasqualeG dAnnunzio Univ Chieti Pescara, Italy
(författare)
-
de Lange, RobertRoche Diagnost GmbH, Germany
(författare)
-
Weidle, Ulrich H.Roche Diagnost GmbH, Germany
(författare)
-
Rotelli, Maria TeresaUniv Aldo Moro, Italy
(författare)
-
Picciariello, ArcangeloUniv Aldo Moro, Italy
(författare)
-
Depalo, RaffaellaOncol Inst IRCCS Giovanni Paolo II, Italy
(författare)
-
Querzoli, PatriziaUniv Ferrara, Italy
(författare)
-
Pedriali, MassimoUniv Hosp, Italy
(författare)
-
Bianchini, EnzoUniv Hosp, Italy
(författare)
-
Angelucci, DomenicoChieti Hosp, Italy
(författare)
-
Pizzicannella, GiuseppeASL2 Chieti Lanciano Vasto, Italy
(författare)
-
Di Loreto, CarlaUniv Udine, Italy
(författare)
-
Piantelli, MauroG dAnnunzio Univ Chieti Pescara, Italy; G dAnnunzio Univ Chieti Pescara, Italy
(författare)
-
Antolini, LauraUniv Milano Bicocca, Italy
(författare)
-
Sun, Xiao-FengLinköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US(Swepub:liu)xiasu45
(författare)
-
Altomare, Donato F.Roche Diagnost GmbH, Germany; Univ Aldo Moro, Italy
(författare)
-
Alberti, SaverioG dAnnunzio Univ Chieti Pescara, Italy; Oncoxx Biotech, Italy; Univ Messina, Italy
(författare)
-
G dAnnunzio Univ Chieti Pescara, Italy; G dAnnunzio Univ Chieti Pescara, ItalyG dAnnunzio Univ Chieti Pescara, Italy; Oncoxx Biotech, Italy
(creator_code:org_t)
Sammanhörande titlar
-
Ingår i:Neoplasia: Elsevier Science INC23:9, s. 898-9111522-80021476-5586
Internetlänk
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Guerra, Emanuela
-
Trerotola, Marco
-
Relli, Valeria
-
Lattanzio, Rossa ...
-
Tripaldi, Romina
-
Vacca, Giovanna
-
visa fler...
-
Ceci, Martina
-
Boujnah, Khoulou ...
-
Garbo, Valeria
-
Moschella, Anton ...
-
Zappacosta, Romi ...
-
Simeone, Pasqual ...
-
de Lange, Robert
-
Weidle, Ulrich H ...
-
Rotelli, Maria T ...
-
Picciariello, Ar ...
-
Depalo, Raffaell ...
-
Querzoli, Patriz ...
-
Pedriali, Massim ...
-
Bianchini, Enzo
-
Angelucci, Domen ...
-
Pizzicannella, G ...
-
Di Loreto, Carla
-
Piantelli, Mauro
-
Antolini, Laura
-
Sun, Xiao-Feng
-
Altomare, Donato ...
-
Alberti, Saverio
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Klinisk medicin
-
och Cancer och onkol ...
- Artiklar i publikationen
-
Neoplasia
- Av lärosätet
-
Linköpings universitet