ELIZA

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501283 occurrences (No.27 in the rank) during 5 years in the PubMed. [cache]

258) Heightened epsin levels in ER-negative human breast cancer are associated with poor relapse-free survival.

--- 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.

--- ABSTRACT END ---

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--- WordNet output for levels --- Overview of noun level The noun level has 8 senses (first 6 from tagged texts) 1. (69) degree, grade, level -- (a position on a scale of intensity or amount or quality; "a moderate grade of intelligence"; "a high level of care is required"; "it is all a matter of degree") 2. (22) grade, level, tier -- (a relative position or degree of value in a graded group; "lumber of the highest grade") 3. (15) degree, level, stage, point -- (a specific identifiable position in a continuum or series or especially in a process; "a remarkable degree of frankness"; "at what stage are the social sciences?") 4. (5) level -- (height above ground; "the water reached ankle level"; "the pictures were at the same level") 5. (1) level, spirit level -- (indicator that establishes the horizontal when a bubble is centered in a tube of liquid) 6. (1) horizontal surface, level -- (a flat surface at right angles to a plumb line; "park the car on the level") 7. level, layer, stratum -- (an abstract place usually conceived as having depth; "a good actor communicates on several levels"; "a simile has at least two layers of meaning"; "the mind functions on many strata simultaneously") 8. floor, level, storey, story -- (a structure consisting of a room or set of rooms at a single position along a vertical scale; "what level is the office on?") Overview of verb level The verb level has 6 senses (first 3 from tagged texts) 1. (4) level -- (aim at; "level criticism or charges at somebody") 2. (1) level, raze, rase, dismantle, tear down, take down, pull down -- (tear down so as to make flat with the ground; "The building was levelled") 3. (1) flush, level, even out, even -- (make level or straight; "level the ground") 4. charge, level, point -- (direct into a position for use; "point a gun"; "He charged his weapon at me") 5. level -- (talk frankly with; lay it on the line; "I have to level with you") 6. level, level off -- (become level or even; "The ground levelled off") --- WordNet end ---