Activation of beta-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters

作者：Li Junlin; Zhou Binhua P^*

来源：BMC Cancer, 2011, 11(1): 49.

DOI：10.1186/1471-2407-11-49

Background: Epithelial-mesenchymal transition (EMT) not only confers tumor cells with a distinct advantage for metastatic dissemination, but also it provides those cells with cancer stem cell-like characters for proliferation and drug resistance. However, the molecular mechanism for maintenance of these stem cell-like traits remains unclear.
Methods: In this study, we induced EMT in breast cancer MCF7 and cervical cancer Hela cells with expression of Twist, a key transcriptional factor of EMT. The morphological changes associated with EMT were analyzed by immunofluorescent staining and Western blotting. The stem cell-like traits associated with EMT were determined by tumorsphere-formation and expression of ALDH1 and CD44 in these cells. The activation of beta-catenin and Akt pathways was examined by Western blotting and luciferase assays.
Results: We found that expression of Twist induced a morphological change associated with EMT. We also found that the cancer stem cell-like traits, such as tumorsphere formation, expression of ALDH1 and CD44, were significantly elevated in Twist-overexpressing cells. Interestingly, we showed that beta-catenin and Akt pathways were activated in these Twist-overexpressing cells. Activation of beta-catenin correlated with the expression of CD44. Knockdown of beta-catenin expression and inhibition of the Akt pathway greatly suppressed the expression of CD44.
Conclusions: Our results indicate that activation of beta-catenin and Akt pathways are required for the sustention of EMT-associated stem cell-like traits.

• 出版日期2011-2-1