Hypoxia induced epithelial-mesenchymal transition and vasculogenic mimicry formation by promoting Bcl-2/Twist1 cooperation

Experimental and Molecular Pathology
Kun LiuNan Zhao

Abstract

Hypoxia plays a pivotal role in tumor progression. The functions of hypoxia and subsequent Bcl-2/Twist1 activation in epithelial-mesenchymal transition (EMT) and vasculogenic mimicry (VM) formation are currently unclear. This study aimed to investigate the role of Bcl-2/Twist1 cooperation in hypoxia-induced EMT and VM formation. In in vitro experiments, we found that hypoxia resulted in co-overexpression of Bcl-2 and Twist1, facilitated Twist1 nuclear translocation and promoted EMT and VM formation. Co-overexpression of Bcl-2 and Twist1 under normoxia could also induce EMT and promote VM formation. Furthermore, blocking Bcl-2 or Twist1 attenuated the effects of hypoxia on EMT progress and VM formation in hepatocellular carcinoma cells. In in vivo experiments, the mechanism by which hypoxia promoted Bcl-2 and Twist1 co-overexpression and induced EMT process and VM formation was demonstrated using murine xenograft models. These results above suggest that hypoxia could activate the cooperation of Bcl-2 and Twist1, Bcl-2 plays an important role in assisting Twist1 nuclear translocation which could change the expression of a wide range of genes and lead to the induction of EMT and VM formation.

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Citations

May 3, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Shuixian LiXiuzhen Han
Feb 14, 2020·Journal of Clinical Medicine·Sun-Wei Guo
Jun 20, 2019·Cancers·Florian CastetJosep Maria Piulats
Oct 16, 2019·Frontiers in Oncology·Lízbeth Ayala-DomínguezMarcela Lizano
Jan 30, 2020·Frontiers in Oncology·Olga N Hernández de la CruzÁngeles Carlos-Reyes
Jul 11, 2019·Oncology Letters·Wei CaoXianghong Yang
Jan 6, 2021·Molecular Cancer·Xiaoxu WeiZhaoyang Zeng
Feb 22, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Ning ZhengJichuang Wang
May 3, 2021·Journal of Translational Medicine·Jingyao CaiZeng Ling
Apr 17, 2020·Life Sciences·Sekaran SaravananVenil N Sumantran

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