Matches in SemOpenAlex for { <https://semopenalex.org/work/W4225114636> ?p ?o ?g. }
- W4225114636 abstract "There is growing evidence that endocytosis plays a pivotal role in cancer metastasis. In this study, we first identified endocytic and metastasis-associated genes (EMGs) and then investigated the biological functions and mechanisms of EMGs.Cancer stem cells (CSCs)-like characteristics were evaluated by tumour limiting dilution assays, three-dimensional (3D) spheroid cancer models. Microarray analysis was used to identify the pathways significantly regulated by mammalian Eps15 homology domain protein 1 (EHD1) knockdown. Mass spectrometry (MS) was performed to identify EHD1-interacting proteins. The function of EHD1 as a regulator of cluster of differentiation 44 (CD44) endocytic recycling and lysosomal degradation was determined by CD44 biotinylation and recycling assays.EHD1 was identified as a significant EMG. Knockdown of EHD1 suppressed CSCs-like characteristics, epithelial-mesenchymal transition (EMT), migration and invasion of lung adenocarcinoma (LUAD) cells by increasing Hippo kinase cascade activation. Conversely, EHD1 overexpression inhibited the Hippo pathway to promote cancer stemness and metastasis. Notably, utilising MS analysis, the CD44 protein was identified as a potential binding partner of EHD1. Furthermore, EHD1 enhanced CD44 recycling and stability. Indeed, silencing of CD44 or disruption of the EHD1/CD44 interaction enhanced Hippo pathway activity and reduced CSCs-like traits, EMT and metastasis. Interestingly, specificity protein 1 (SP1), a known downstream target gene of the Hippo-TEA-domain family members 1 (TEAD1) pathway, was found to directly bind to the EHD1 promoter region and induce its expression. Among clinical specimens, the EHD1 expression level in LUAD tissues of metastatic patients was higher than that of non-metastatic patients.Our findings emphasise that EHD1 might be a potent anti-metastatic target and present a novel regulatory mechanism by which the EHD1/CD44/Hippo/SP1 positive feedback circuit plays pivotal roles in coupling modules of CSCs-like properties and EMT in LUAD. Targeting this loop may serve as a remedy for patients with advanced metastatic LUAD." @default.
- W4225114636 created "2022-05-01" @default.
- W4225114636 creator A5007322337 @default.
- W4225114636 creator A5029225610 @default.
- W4225114636 creator A5031105368 @default.
- W4225114636 creator A5036415591 @default.
- W4225114636 creator A5039440121 @default.
- W4225114636 creator A5045891159 @default.
- W4225114636 creator A5057561095 @default.
- W4225114636 creator A5062518136 @default.
- W4225114636 creator A5073787845 @default.
- W4225114636 creator A5077232555 @default.
- W4225114636 creator A5078687129 @default.
- W4225114636 creator A5090306446 @default.
- W4225114636 date "2022-04-01" @default.
- W4225114636 modified "2023-10-16" @default.
- W4225114636 title "A novel EHD1/CD44/Hippo/SP1 positive feedback loop potentiates stemness and metastasis in lung adenocarcinoma" @default.
- W4225114636 cites W1500053947 @default.
- W4225114636 cites W1513237282 @default.
- W4225114636 cites W1966231010 @default.
- W4225114636 cites W1966311581 @default.
- W4225114636 cites W1974829226 @default.
- W4225114636 cites W1984518509 @default.
- W4225114636 cites W1991886980 @default.
- W4225114636 cites W1995160678 @default.
- W4225114636 cites W1995857416 @default.
- W4225114636 cites W2005356516 @default.
- W4225114636 cites W2014691022 @default.
- W4225114636 cites W2019732936 @default.
- W4225114636 cites W2022233074 @default.
- W4225114636 cites W2051974311 @default.
- W4225114636 cites W2058374433 @default.
- W4225114636 cites W2068762252 @default.
- W4225114636 cites W2072246040 @default.
- W4225114636 cites W2082946777 @default.
- W4225114636 cites W2085271514 @default.
- W4225114636 cites W2087728854 @default.
- W4225114636 cites W2100641053 @default.
- W4225114636 cites W2114602831 @default.
- W4225114636 cites W2114906733 @default.
- W4225114636 cites W2135149818 @default.
- W4225114636 cites W2156130718 @default.
- W4225114636 cites W2163113687 @default.
- W4225114636 cites W2164358503 @default.
- W4225114636 cites W2214517872 @default.
- W4225114636 cites W2223413920 @default.
- W4225114636 cites W2235523093 @default.
- W4225114636 cites W2251438188 @default.
- W4225114636 cites W2266814182 @default.
- W4225114636 cites W2346363069 @default.
- W4225114636 cites W2397392763 @default.
- W4225114636 cites W2409025151 @default.
- W4225114636 cites W2415046758 @default.
- W4225114636 cites W2463195918 @default.
- W4225114636 cites W2490757425 @default.
- W4225114636 cites W2515237737 @default.
- W4225114636 cites W2516249363 @default.
- W4225114636 cites W2524428698 @default.
- W4225114636 cites W2577408658 @default.
- W4225114636 cites W2589702300 @default.
- W4225114636 cites W2591710757 @default.
- W4225114636 cites W2600626962 @default.
- W4225114636 cites W2775387952 @default.
- W4225114636 cites W2793586303 @default.
- W4225114636 cites W2806713886 @default.
- W4225114636 cites W2809413985 @default.
- W4225114636 cites W2883298217 @default.
- W4225114636 cites W2890393959 @default.
- W4225114636 cites W2891780076 @default.
- W4225114636 cites W2899861913 @default.
- W4225114636 cites W2902153050 @default.
- W4225114636 cites W2903083130 @default.
- W4225114636 cites W2907642042 @default.
- W4225114636 cites W2908925187 @default.
- W4225114636 cites W2945386387 @default.
- W4225114636 cites W2946136156 @default.
- W4225114636 cites W2968336221 @default.
- W4225114636 cites W2987791246 @default.
- W4225114636 cites W2996626242 @default.
- W4225114636 cites W2999295226 @default.
- W4225114636 cites W3012255501 @default.
- W4225114636 cites W3034338277 @default.
- W4225114636 cites W3041926928 @default.
- W4225114636 cites W3044237032 @default.
- W4225114636 cites W3087662485 @default.
- W4225114636 cites W3088563315 @default.
- W4225114636 cites W3088735400 @default.
- W4225114636 cites W3106046349 @default.
- W4225114636 cites W3112895239 @default.
- W4225114636 cites W3119005666 @default.
- W4225114636 cites W3119162394 @default.
- W4225114636 cites W3128646645 @default.
- W4225114636 cites W3158997416 @default.
- W4225114636 cites W3174743744 @default.
- W4225114636 cites W4225114636 @default.
- W4225114636 cites W2798323364 @default.
- W4225114636 doi "https://doi.org/10.1002/ctm2.836" @default.
- W4225114636 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35485206" @default.
- W4225114636 hasPublicationYear "2022" @default.
- W4225114636 type Work @default.