scholarly journals Stage of Breast Cancer Progression Influences Cellular Response to Activation of the WNT/Planar Cell Polarity Pathway

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Connor D. MacMillan ◽  
Hon S. Leong ◽  
David W. Dales ◽  
Amy E. Robertson ◽  
John D. Lewis ◽  
...  
2016 ◽  
Vol 117 (10) ◽  
pp. 2215-2223 ◽  
Author(s):  
Carlis Rejon ◽  
Maia Al-Masri ◽  
Luke McCaffrey

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 12
Author(s):  
Megharani Mahajan ◽  
Sandhya Sitasawad

Hypoxia and oxidative stress significantly contribute to breast cancer (BC) progression. Although hypoxia-inducible factor 1α (Hif-1α) is considered a key effector of the cellular response to hypoxia, nuclear factor erythroid 2–related factor 2 (Nrf2), a master antioxidant transcription factor, is a crucial factor essential for Hif-1α-mediated hypoxic responses. Hence, targeting Nrf2 could provide new treatment strategies for cancer therapy. miRNAs are potential regulators of hypoxia-responsive genes. In a quest to identify novel hypoxia-regulated miRNAs involved in the regulation of Nrf2, we found that miR-140-5p significantly affects the expression of Nrf2 under hypoxia. In our study, miR-140-5p expression is downregulated in BC cells under hypoxic conditions. We have identified Nrf2 as a direct target of miR-140-5p, as confirmed by the luciferase assay. Knockdown of miR-140-5p under normoxic conditions significantly enhanced Nrf2/HO-1 signaling and tumor growth, angiogenesis, migration, and invasion in BC. In contrast, overexpression of miR-140-5p under hypoxic conditions revealed opposite results. Further silencing Nrf2 expression mimicked the miR-140-5p-induced anti-tumor effects. Consistent with the knockdown of miR-140-5p in vitro, mice injected with miR-140-5p-KD cells exhibited dramatically reduced miR-140-5p levels, increased Nrf2 levels, and increased tumor growth. In contrast, tumor growth is potently suppressed in mice injected with miR-140-5p-OE cells. Collectively, the above results demonstrate the importance of the Nrf2/HO-1 axis in cancer progression and, thus, targeting Nrf2 by miR-140-5p could be a better strategy for the treatment of Nrf2-driven breast cancer progression.


2014 ◽  
Vol 25 (15) ◽  
pp. 2291-2304 ◽  
Author(s):  
Alison E. Meyer ◽  
Catherine E. Gatza ◽  
Tam How ◽  
Mark Starr ◽  
Andrew B. Nixon ◽  
...  

The majority of breast cancers originate from the highly polarized luminal epithelial cells lining the breast ducts. However, cell polarity is often lost during breast cancer progression. The type III transforming growth factor-β cell surface receptor (TβRIII) functions as a suppressor of breast cancer progression and also regulates the process of epithelial-to-mesenchymal transition (EMT), a consequence of which is the loss of cell polarity. Many cell surface proteins exhibit polarized expression, being targeted specifically to the apical or basolateral domains. Here we demonstrate that TβRIII is basolaterally localized in polarized breast epithelial cells and that disruption of the basolateral targeting of TβRIII through a single amino acid mutation of proline 826 in the cytosolic domain results in global loss of cell polarity through enhanced EMT. In addition, the mistargeting of TβRIII results in enhanced proliferation, migration, and invasion in vitro and enhanced tumor formation and invasion in an in vivo mouse model of breast carcinoma. These results suggest that proper localization of TβRIII is critical for maintenance of epithelial cell polarity and phenotype and expand the mechanisms by which TβRIII prevents breast cancer initiation and progression.


Oncogene ◽  
2011 ◽  
Vol 31 (32) ◽  
pp. 3696-3708 ◽  
Author(s):  
J N Anastas ◽  
T L Biechele ◽  
M Robitaille ◽  
J Muster ◽  
K H Allison ◽  
...  

2014 ◽  
Author(s):  
Mattia Capulli ◽  
Adriano Angelucci ◽  
Anna Teti ◽  
Patrizia Sanita ◽  
Luca Ventura ◽  
...  

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