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Early Growth Response 1 Induces Epithelial-to-mesenchymal Transition via Snail

Egr-1-Snail 작용에 의한 epithelial-to-mesenchymal transition 유도

  • Jeon, Hyun Min (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Lee, Su Yeon (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Ju, Min Kyung (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Park, Hye Gyeong (Nanobiotechnology Center, Pusan National University) ;
  • Kang, Ho Sung (Department of Molecular Biology, College of Natural Sciences, Pusan National University)
  • 전현민 (부산대학 자연과학대학 분자생물학과) ;
  • 이수연 (부산대학 자연과학대학 분자생물학과) ;
  • 주민경 (부산대학 자연과학대학 분자생물학과) ;
  • 박혜경 (한국나노바이오테크놀러지센터) ;
  • 강호성 (부산대학 자연과학대학 분자생물학과)
  • Received : 2013.07.25
  • Accepted : 2013.08.08
  • Published : 2013.08.30

Abstract

The epithelial-to-mesenchymal transition (EMT) plays an essential role in embryogenesis and is involved in tumor metastasis and invasion; it significantly contributes to tumor progression and aggressiveness. The EMT is characterized by a loss of epithelial cell polarity as a result of the reduced expression of epithelial E-cadherin, a hallmark of the EMT, and the acquisition of mesenchymal-like cell morphology. Reactive oxygen species (ROS) such as $O_2{^-}$, $H_2O_2$, and $OH^-$ have been demonstrated to induce the EMT; although Snail is involved in ROS-induced EMT by transcriptionally repressing E-cadherin, its mechanism is not fully understood. In this study, we examined the effects of early growth response 1 (Egr-1) overexpression in noninvasive breast tumor cell line MCF-7 cells. Upon Egr-1 overexpression, MCF-7 cells lost epithelial cell polarity and became more spindle-shaped, indicating that Egr-1 may induce EMT. We found that Snail is implicated in Egr-1 induced EMT. We further demonstrate that the Egr-1-Snail axis is activated by ROS and plays a critical role(s) in ROS-induced EMT.

Epithelial-to-mesenchymal transition (EMT)는 embryogenesis에서 중요한 역할을 하며 tumor metastasis, invasion에도 관여함으로써 tumor progression 및 aggressiveness에 기여한다. EMT는 EMT hallmark인 epithelial E-cadherin의 발현 감소와 mesenchymal-like cell morphology를 획득함으로써 epithelial cell polarity를 잃어버리는 특징을 가지고 있다. $O_2{^-}$, $H_2O_2$, $OH^-$와 같은 활성산소가 EMT를 유도하는 것으로 알려져 있다. Snail이 E-cadherin의 발현을 억제함으로써 ROS에 의한 EMT에 관여하는 것으로 알려져 있으나, 그 기작은 완전히 밝혀져 있지 않다. 본 연구에서는, noninvasive breast tumor cell line인 MCF-7 세포에 Egr-1을 과발현시킨 후 그 영향을 조사하였다. Egr-1이 과발현되면, MCF-7 세포는 epithelial cell polarity를 잃고 spindle-shaped로 변화되므로, Egr-1이 EMT를 유도할 가능성이 대두되었다. 또한 Snail이 Egr-1에 의한 EMT에 관여함을 확인하였다. 나아가, 본 연구진은 Egr-1-Snail axis가 ROS에 의해 활성화 되고, ROS에 의한 EMT에서 중요한 역할을 함을 발견하였다.

Keywords

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