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return kwic search for development out of >500 occurrences
383385 occurrences (No.47 in the rank) during 5 years in the PubMed. [cache]

354) 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.

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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)207 of	(6)5 is	(11)3 process	(16)2 process,
(2)74 and	(7)5 to	(12)2 aid	(17)2 programmes
(3)68 null	(8)4 has	(13)2 but	(18)2 programs
(4)13 in	(9)4 the	(14)2 for	(19)2 research
(5)5 Goals	(10)3 are	(15)2 implementation	(20)2 studies

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--- WordNet output for development --- =>発達, 開発, 産物, 進展 Overview of noun development The noun development has 9 senses (first 7 from tagged texts) 1. (52) development -- (act of improving by expanding or enlarging or refining; "he congratulated them on their development of a plan to meet the emergency"; "they funded research and development") 2. (46) development, evolution -- (a process in which something passes by degrees to a different stage (especially a more advanced or mature stage); "the development of his ideas took many years"; "the evolution of Greek civilization"; "the slow development of her skill as a writer") 3. (11) growth, growing, maturation, development, ontogeny, ontogenesis -- ((biology) the process of an individual organism growing organically; a purely biological unfolding of events involved in an organism changing gradually from a simple to a more complex level; "he proposed an indicator of osseous development in children") 4. (9) development -- (a recent event that has some relevance for the present situation; "recent developments in Iraq"; "what a revolting development!") 5. (7) exploitation, development -- (the act of making some area of land or water more profitable or productive or useful; "the development of Alaskan resources"; "the exploitation of copper deposits") 6. (6) development -- (a district that has been developed to serve some purpose; "such land is practical for small park developments") 7. (4) development -- (a state in which things are improving; the result of developing (as in the early part of a game of chess); "after he saw the latest development he changed his mind and became a supporter"; "in chess your should take care of your development before moving your queen") 8. development, developing -- (processing a photosensitive material in order to make an image visible; "the development and printing of his pictures took only two hours") 9. development -- ((music) the section of a composition or movement (especially in sonata form) where the major musical themes are developed and elaborated) --- WordNet end ---