scholarly journals Cancer stem cell property and gene signature in bone-metastatic Breast Cancer cells

2020 ◽  
Vol 16 (14) ◽  
pp. 2580-2594
Author(s):  
An Luo ◽  
Yue Xu ◽  
Shujun Li ◽  
Jinxia Bao ◽  
Jinhui Lü ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Metastatic Breast Cancer ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Gene Signature ◽  
Stem Cell Property ◽  
Cell Property

scholarly journals Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells

Nature ◽  
2015 ◽  
Vol 526 (7571) ◽  
pp. 131-135 ◽  
Author(s):  
Devon A. Lawson ◽  
Nirav R. Bhakta ◽  
Kai Kessenbrock ◽  
Karin D. Prummel ◽  
Ying Yu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Metastatic Breast Cancer ◽  
Single Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Single Cell Analysis ◽  
Metastatic Breast ◽  
Cell Analysis

scholarly journals The FBXW2–MSX2–SOX2 axis regulates stem cell property and drug resistance of cancer cells

2019 ◽  
Vol 116 (41) ◽  
pp. 20528-20538 ◽  
Author(s):  
Yuan Yin ◽  
Chuan-Ming Xie ◽  
Hua Li ◽  
Mingjia Tan ◽  
Guoan Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Stem Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
E3 Ligase ◽  
Stem Cell Property ◽  
Sox2 Expression ◽  
Cell Property

SOX2 is a key transcription factor that plays critical roles in maintaining stem cell property and conferring drug resistance. However, the underlying mechanisms by which SOX2 level is precisely regulated remain elusive. Here we report that MLN4924, also known as pevonedistat, a small-molecule inhibitor of neddylation currently in phase II clinical trials, down-regulates SOX2 expression via causing accumulation of MSX2, a known transcription repressor of SOX2 expression. Mechanistic characterization revealed that MSX2 is a substrate of FBXW2 E3 ligase. FBXW2 binds to MSX2 and promotes MSX2 ubiquitylation and degradation. Likewise, FBXW2 overexpression shortens the protein half-life of MSX2, whereas FBXW2 knockdown extends it. We further identified hypoxia as a stress condition that induces VRK2 kinase to facilitate MSX2–FBXW2 binding and FBXW2-mediated MSX2 ubiquitylation and degradation, leading to SOX2 induction via derepression. Biologically, expression of FBXW2 or SOX2 promotes tumor sphere formation, which is blocked by MSX2 expression. By down-regulating SOX2 through inactivation of FBXW2 E3 ligase, MLN4924 sensitizes breast cancer cells to tamoxifen in both in vitro and in vivo cancer cell models. Thus, a negative cascade of the FBXW2–MSX2–SOX2 axis was established, which regulates stem cell property and drug resistance. Finally, an inverse correlation of expression was found between FBXW2 and MSX2 in lung and breast cancer tissues. Collectively, our study revealed an anticancer mechanism of MLN4924. By inactivating FBXW2, MLN4924 caused MSX2 accumulation to repress SOX2 expression, leading to suppression of stem cell property and sensitization of breast cancer cells to tamoxifen.

scholarly journals The migration of metastatic breast cancer cells is regulated by matrix stiffness via YAP signalling

Heliyon ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. e06252
Author(s):  
Wei Chen ◽  
Shihyun Park ◽  
Chrishma Patel ◽  
Yuxin Bai ◽  
Karim Henary ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Matrix Stiffness
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