Matches in SemOpenAlex for { <https://semopenalex.org/work/W4377029448> ?p ?o ?g. }
Showing items 1 to 68 of
68
with 100 items per page.
- W4377029448 abstract "<div>Abstract<p>Tumor metastasis is a complex process. A better understanding of the mechanistic underpinnings of the metastatic cascade could uncover approaches to better prevent and target metastases. Here, we integrated transcriptomic profiling in primary esophageal squamous cell carcinoma (ESCC) and matched lymph node metastatic tissues and genome-wide CRISPR/Cas9 functional screening to identify the key drivers of cancer metastasis. Anoctamin 1 (ANO1) expression was found to be elevated in primary tumors and further increased in metastatic tissues. High expression of ANO1 was associated with poor patient survival, and ANO1 overexpression promoted cancer invasion and metastasis. Mechanistically, ANO1 inactivated the LXR pathway and increased intracellular cholesterol accumulation by interacting with JUN to repress the transcription of cholesterol hydroxylase, CYP27A1. In a paracrine manner, IL1β secreted from ANO1-expressing ESCC cancer cells activated NF-κB signaling in fibroblasts to stimulate production of the chemokine CCL1, which in turn enhanced invasion of ESCC cancer cells. Furthermore, molecular docking and <i>in silico</i> screening of 1,500,000 small molecules identified K786–4469 as a lead compound that targeted ANO1 and suppressed cancer metastasis <i>in vitro</i> and <i>in vivo</i>. Overall, these findings uncover a noncanonical function of ANO1 in regulating cholesterol metabolism and fibroblast function, revealing ANO1 as a potential prognostic biomarker and therapeutic target for metastatic ESCC.</p>Significance:<p>Metastatic cancer cells upregulate ANO1 to activate cell-intrinsic and -extrinsic mechanisms that alter cholesterol metabolism and stimulate fibroblasts, which can be targeted with ANO1 inhibitors to inhibit metastatic growth.</p><p><i><a href=https://aacrjournals.org/cancerres/article/doi/10.1158/0008-5472.CAN-23-0624 target=_blank>See related commentary by Singh and Mehla, p. 1759</a></i></p></div>" @default.
- W4377029448 created "2023-05-19" @default.
- W4377029448 creator A5009493454 @default.
- W4377029448 creator A5022034847 @default.
- W4377029448 creator A5034596086 @default.
- W4377029448 creator A5038326454 @default.
- W4377029448 creator A5038945839 @default.
- W4377029448 creator A5052059747 @default.
- W4377029448 creator A5059326007 @default.
- W4377029448 creator A5069657399 @default.
- W4377029448 creator A5071066805 @default.
- W4377029448 creator A5081267732 @default.
- W4377029448 date "2023-06-02" @default.
- W4377029448 modified "2023-10-18" @default.
- W4377029448 title "Data from ANO1 Reprograms Cholesterol Metabolism and the Tumor Microenvironment to Promote Cancer Metastasis" @default.
- W4377029448 doi "https://doi.org/10.1158/0008-5472.c.6653429" @default.
- W4377029448 hasPublicationYear "2023" @default.
- W4377029448 type Work @default.
- W4377029448 citedByCount "0" @default.
- W4377029448 crossrefType "posted-content" @default.
- W4377029448 hasAuthorship W4377029448A5009493454 @default.
- W4377029448 hasAuthorship W4377029448A5022034847 @default.
- W4377029448 hasAuthorship W4377029448A5034596086 @default.
- W4377029448 hasAuthorship W4377029448A5038326454 @default.
- W4377029448 hasAuthorship W4377029448A5038945839 @default.
- W4377029448 hasAuthorship W4377029448A5052059747 @default.
- W4377029448 hasAuthorship W4377029448A5059326007 @default.
- W4377029448 hasAuthorship W4377029448A5069657399 @default.
- W4377029448 hasAuthorship W4377029448A5071066805 @default.
- W4377029448 hasAuthorship W4377029448A5081267732 @default.
- W4377029448 hasConcept C121608353 @default.
- W4377029448 hasConcept C170493617 @default.
- W4377029448 hasConcept C2776107976 @default.
- W4377029448 hasConcept C2779013556 @default.
- W4377029448 hasConcept C3020616263 @default.
- W4377029448 hasConcept C502942594 @default.
- W4377029448 hasConcept C54355233 @default.
- W4377029448 hasConcept C55493867 @default.
- W4377029448 hasConcept C7876069 @default.
- W4377029448 hasConcept C86803240 @default.
- W4377029448 hasConcept C96232424 @default.
- W4377029448 hasConceptScore W4377029448C121608353 @default.
- W4377029448 hasConceptScore W4377029448C170493617 @default.
- W4377029448 hasConceptScore W4377029448C2776107976 @default.
- W4377029448 hasConceptScore W4377029448C2779013556 @default.
- W4377029448 hasConceptScore W4377029448C3020616263 @default.
- W4377029448 hasConceptScore W4377029448C502942594 @default.
- W4377029448 hasConceptScore W4377029448C54355233 @default.
- W4377029448 hasConceptScore W4377029448C55493867 @default.
- W4377029448 hasConceptScore W4377029448C7876069 @default.
- W4377029448 hasConceptScore W4377029448C86803240 @default.
- W4377029448 hasConceptScore W4377029448C96232424 @default.
- W4377029448 hasLocation W43770294481 @default.
- W4377029448 hasOpenAccess W4377029448 @default.
- W4377029448 hasPrimaryLocation W43770294481 @default.
- W4377029448 hasRelatedWork W1532133662 @default.
- W4377029448 hasRelatedWork W2123242217 @default.
- W4377029448 hasRelatedWork W2154708791 @default.
- W4377029448 hasRelatedWork W2898196535 @default.
- W4377029448 hasRelatedWork W2898913749 @default.
- W4377029448 hasRelatedWork W2913256810 @default.
- W4377029448 hasRelatedWork W3016597179 @default.
- W4377029448 hasRelatedWork W3091643843 @default.
- W4377029448 hasRelatedWork W4283771460 @default.
- W4377029448 hasRelatedWork W4304116770 @default.
- W4377029448 isParatext "false" @default.
- W4377029448 isRetracted "false" @default.
- W4377029448 workType "article" @default.