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return kwic search for role out of >500 occurrences
507580 occurrences (No.24 in the rank) during 5 years in the PubMed. [cache]

483) Our findings established the pivotal role epsins played in promoting breast cancer.

--- ABSTRACT ---

PMID:32960814 DOI:10.1172/JCI129374

2021 The Journal of clinical investigation

* Epsins 1 and 2 promote NEMO linear ubiquitination via LUBAC to drive breast cancer development.

- Estrogen receptor-negative (ER-negative) breast cancer is thought to be more malignant and devastating than ER-positive breast cancer. ER-negative breast cancer exhibits elevated NF-κB activity, but how this abnormally high NF-κB activity is maintained is poorly understood. The importance of linear ubiquitination, which is generated by the linear ubiquitin chain assembly complex (LUBAC), is increasingly appreciated in NF-κB signaling, which regulates cell activation and death. Here, we showed that epsin proteins, a family of ubiquitin-binding endocytic adaptors, interacted with LUBAC via its ubiquitin-interacting motif and bound LUBAC's bona fide substrate NEMO via its N-terminal homolog (ENTH) domain. Furthermore, epsins promoted NF-κB essential modulator (NEMO) linear ubiquitination and served as scaffolds for recruiting other components of the IκB kinase (IKK) complex, resulting in the heightened IKK activation and sustained NF-κB signaling essential for the development of ER-negative breast cancer. Heightened epsin levels in ER-negative human breast cancer are associated with poor relapse-free survival. We showed that transgenic and pharmacological approaches eliminating epsins potently impeded breast cancer development in both spontaneous and patient-derived xenograft breast cancer mouse models. Our findings established the pivotal role epsins played in promoting breast cancer. Thus, targeting epsins may represent a strategy to restrain NF-κB signaling and provide an important perspective into ER-negative breast cancer treatment.

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(1)215 of	(4)9 null	(7)5 as
(2)199 in	(5)8 and	(8)3 by
(3)23 for	(6)6 that	(9)2 is

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--- WordNet output for role --- =>役目, 役割, 任務, 職務, 役 Overview of noun role The noun role has 4 senses (first 4 from tagged texts) 1. (34) function, office, part, role -- (the actions and activities assigned to or required or expected of a person or group; "the function of a teacher"; "the government must do its part"; "play its role") 2. (10) character, role, theatrical role, part, persona -- (an actor's portrayal of someone in a play; "she played the part of Desdemona") 3. (8) function, purpose, role, use -- (what something is used for; "the function of an auger is to bore holes"; "ballet is beautiful but what use is it?") 4. (6) role -- (normal or customary activity of a person in a particular social setting; "what is your role on the team?") --- WordNet end ---