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      <dc:title>TGFβ Governs the Pleiotropic Activity of NDRG1 in Triple-Negative Breast Cancer Progression</dc:title>
      <dc:creator>López Tejada, Araceli</dc:creator>
      <dc:creator>Griñán Lisón, Carmen</dc:creator>
      <dc:creator>González González, Adrián</dc:creator>
      <dc:creator>Cara, Francisca E.</dc:creator>
      <dc:creator>Blaya Cánovas, José Lucas</dc:creator>
      <dc:creator>Navarro Ocón, Alba</dc:creator>
      <dc:creator>Valenzuela Torres, María</dc:creator>
      <dc:creator>Parra López, Marisa</dc:creator>
      <dc:creator>Calahorra, Jesús</dc:creator>
      <dc:creator>Blancas López-Barajas, María Isabel</dc:creator>
      <dc:creator>Marchal Corrales, Juan Antonio</dc:creator>
      <dc:creator>Granados Principal, Sergio</dc:creator>
      <dc:subject>Cancer stem cell</dc:subject>
      <dc:subject>NDRG1</dc:subject>
      <dc:subject>TGFβ</dc:subject>
      <dc:subject>Triple-negative breast cancer</dc:subject>
      <dc:subject>Tumor progression</dc:subject>
      <dc:description>In triple-negative breast cancer (TNBC), the pleiotropic NDRG1 (N-Myc downstream regulated gene 1)&#xd;
promotes progression and worse survival, yet contradictory results were documented, and the mechanisms&#xd;
remain unknown. Phosphorylation and localization could drive NDRG1 pleiotropy, nonetheless, their role in&#xd;
TNBC progression and clinical outcome was not investigated. We found enhanced p-NDRG1 (Thr346) by&#xd;
TGFβ1 and explored whether it drives NDRG1 pleiotropy and TNBC progression. In tissue microarrays of 81&#xd;
TNBC patients, we identified that staining and localization of NDRG1 and p-NDRG1 (Thr346) are biomarkers&#xd;
and risk factors associated with shorter overall survival. We found that TGFβ1 leads NDRG1, downstream of&#xd;
GSK3β, and upstream of NF-κB, to differentially regulate migration, invasion, epithelial-mesenchymal transition,&#xd;
tumor initiation, and maintenance of different populations of cancer stem cells (CSCs), depending on the&#xd;
progression stage of tumor cells, and the combination of TGFβ and GSK3β inhibitors impaired CSCs. The&#xd;
present study revealed the striking importance to assess both total NDRG1 and p-NDRG1 (Thr346)&#xd;
positiveness and subcellular localization to evaluate patient prognosis and their stratification. NDRG1&#xd;
pleiotropy is driven by TGFβ to differentially promote metastasis and/or maintenance of CSCs at different&#xd;
stages of tumor progression, which could be abrogated by the inhibition of TGFβ and GSK3β.</dc:description>
      <dc:date>2023-01-19T07:47:56Z</dc:date>
      <dc:date>2023-01-19T07:47:56Z</dc:date>
      <dc:date>2023-01-01</dc:date>
      <dc:type>journal article</dc:type>
      <dc:identifier>López-Tejada, A... [et al.] (2023). TGFβ Governs the Pleiotropic Activity of NDRG1 in Triple-Negative Breast Cancer Progression. International Journal of Biological Sciences, 19(1), 204-224. [https://doi.org/10.7150/ijbs.78738]</dc:identifier>
      <dc:identifier>https://hdl.handle.net/10481/79130</dc:identifier>
      <dc:identifier>10.7150/ijbs.78738</dc:identifier>
      <dc:language>eng</dc:language>
      <dc:rights>http://creativecommons.org/licenses/by/4.0/</dc:rights>
      <dc:rights>open access</dc:rights>
      <dc:rights>Atribución 4.0 Internacional</dc:rights>
      <dc:publisher>Ivyspring</dc:publisher>
   </ow:Publication>
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