@misc{10481/79130,
year = {2023},
month = {1},
url = {https://hdl.handle.net/10481/79130},
abstract = {In triple-negative breast cancer (TNBC), the pleiotropic NDRG1 (N-Myc downstream regulated gene 1)
promotes progression and worse survival, yet contradictory results were documented, and the mechanisms
remain unknown. Phosphorylation and localization could drive NDRG1 pleiotropy, nonetheless, their role in
TNBC progression and clinical outcome was not investigated. We found enhanced p-NDRG1 (Thr346) by
TGFβ1 and explored whether it drives NDRG1 pleiotropy and TNBC progression. In tissue microarrays of 81
TNBC patients, we identified that staining and localization of NDRG1 and p-NDRG1 (Thr346) are biomarkers
and risk factors associated with shorter overall survival. We found that TGFβ1 leads NDRG1, downstream of
GSK3β, and upstream of NF-κB, to differentially regulate migration, invasion, epithelial-mesenchymal transition,
tumor initiation, and maintenance of different populations of cancer stem cells (CSCs), depending on the
progression stage of tumor cells, and the combination of TGFβ and GSK3β inhibitors impaired CSCs. The
present study revealed the striking importance to assess both total NDRG1 and p-NDRG1 (Thr346)
positiveness and subcellular localization to evaluate patient prognosis and their stratification. NDRG1
pleiotropy is driven by TGFβ to differentially promote metastasis and/or maintenance of CSCs at different
stages of tumor progression, which could be abrogated by the inhibition of TGFβ and GSK3β.},
organization = {Instituto de Salud Carlos III
European Commission	PI15/00336	
PI19/01533	
CP14/00197	
CP19/00029	
PIE16/00045},
organization = {Ministry of Science and Innovation, Spain (MICINN)},
organization = {Instituto de Salud Carlos III},
organization = {Spanish Government	RTI2018.101309B-C22},
organization = {Chair "Doctors Galera-Requena in cancer stem cell research"	CMC-CTS963},
organization = {European Regional Development Fund (European Union)},
organization = {Ministerio de Universidades	FPU19/04450},
organization = {Junta de Andalucia	RH-0139-2020},
organization = {Sistema Nacional de Garantia Juvenil (Fondo Social Europeo)	8064},
organization = {Junta de Andalucia, Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades	DOC_01686},
organization = {Fundacion Cientifica Asociacion Espanola Contra el Cancer, Junta Provincial de Jaen (AECC)	PRDJA19001BLAY},
publisher = {Ivyspring},
keywords = {Cancer stem cell},
keywords = {NDRG1},
keywords = {TGFβ},
keywords = {Triple-negative breast cancer},
keywords = {Tumor progression},
title = {TGFβ Governs the Pleiotropic Activity of NDRG1 in Triple-Negative Breast Cancer Progression},
doi = {10.7150/ijbs.78738},
author = {López Tejada, Araceli and Griñán Lisón, Carmen and González González, Adrián and Cara, Francisca E. and Blaya Cánovas, José Lucas and Navarro Ocón, Alba and Valenzuela Torres, María and Parra López, Marisa and Calahorra, Jesús and Blancas López-Barajas, María Isabel and Marchal Corrales, Juan Antonio and Granados Principal, Sergio},
}