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10.18632/oncotarget.11062

http://scihub22266oqcxt.onion/10.18632/oncotarget.11062
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C5308634!5308634!27506933
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suck abstract from ncbi


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pmid27506933      Oncotarget 2016 ; 7 (38): 61036-53
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  • NUMB negatively regulates the epithelial-mesenchymal transition of triple-negative breast cancer by antagonizing Notch signaling #MMPMID27506933
  • Zhang J; Shao X; Sun H; Liu K; Ding Z; Chen J; Fang L; Su W; Hong Y; Li H; Li H
  • Oncotarget 2016[Sep]; 7 (38): 61036-53 PMID27506933show ga
  • Triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer with higher rates of early relapse and metastasis, is frequently associated with aberrant activation of epithelial-mesenchymal transition (EMT). Nonetheless, how EMT is initiated and regulated during TNBC progression is not well understood. Here, we report that NUMB is a negative regulator of EMT in both human mammary epithelial cells and breast cancer cells. Reduced NUMB expression was significantly associated with elevated EMT in TNBC. Conversely, overexpression of NUMB strongly attenuated the EMT program and metastasis of TNBC cell lines. Interestingly, we showed that NUMB employs different molecular mechanisms to regulate EMT. In normal mammary epithelial cells and breast cancer cells expressing wild-type p53, NUMB suppressed EMT by stabilizing p53. However, in TNBC cells, loss of NUMB facilitated the EMT program by activating Notch signaling. Consistent with these findings, low NUMB expression and high Notch activity were significantly correlated with the TNBC subtype in patients. Collectively, these findings reveal novel molecular mechanisms of NUMB in the regulation of breast tumor EMT, especially in TNBC.
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