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UBTD1 is a mechano‐regulator controlling cancer aggressiveness
Author(s) -
Torrino Stéphanie,
Roustan FrançoisRené,
Kaminski Lisa,
Bertero Thomas,
Pisano Sabrina,
Ambrosetti Damien,
Dufies Maeva,
Uhler Jay P,
Lemichez Emmanuel,
Mettouchi Amel,
Gesson Maeva,
Laurent Kathiane,
Gaggioli Cedric,
Michiels JeanFrancois,
Lamaze Christophe,
Bost Frédéric,
Clavel Stéphan
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201846570
Subject(s) - regulator , cancer , microbiology and biotechnology , chemistry , biology , biochemistry , genetics , gene
Ubiquitin domain‐containing protein 1 ( UBTD 1) is highly evolutionary conserved and has been described to interact with E2 enzymes of the ubiquitin–proteasome system. However, its biological role and the functional significance of this interaction remain largely unknown. Here, we demonstrate that depletion of UBTD 1 drastically affects the mechanical properties of epithelial cancer cells via RhoA activation and strongly promotes their aggressiveness. On a stiff matrix, UBTD 1 expression is regulated by cell–cell contacts, and the protein is associated with β‐catenin at cell junctions. Yes‐associated protein ( YAP ) is a major cell mechano‐transducer, and we show that UBTD 1 is associated with components of the YAP degradation complex. Interestingly, UBTD 1 promotes the interaction of YAP with its E3 ubiquitin ligase β‐Tr CP . Consequently, in cancer cells, UBTD 1 depletion decreases YAP ubiquitylation and triggers robust ROCK 2‐dependent YAP activation and downstream signaling. Data from lung and prostate cancer patients further corroborate the in cellulo results, confirming that low levels of UBTD 1 are associated with poor patient survival, suggesting that biological functions of UBTD 1 could be beneficial in limiting cancer progression.