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Induction and Analysis of Epithelial to Mesenchymal Transition
10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

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Dlx-2 is implicated in TGF-β- and Wnt-induced epithelial-mesenchymal, glycolytic switch, and mitochondrial repression

Su Yeon Lee1, Hyun Min Jeon1, Min Kyung Ju1

  • 1Department of Molecular Biology, College of Natural Sciences, Pusan National University, Pusan 609-735, Republic of Korea.

International Journal of Oncology
|February 6, 2015
PubMed

Insights

Distal-less homeobox 2 (Dlx-2) drives tumor progression by activating Snail, promoting epithelial-mesenchymal transition (EMT) and a metabolic switch. This process also involves the suppression of mitochondrial respiration, impacting cancer development.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Biology

Background:

  • Epithelial-mesenchymal transition (EMT) and altered cellular metabolism, particularly the Warburg effect (glycolytic switch), are critical hallmarks of tumor progression.
  • The interplay between EMT and oncogenic metabolism is increasingly recognized as a driver of cancer development and metastasis.

Purpose of the Study:

  • To investigate the role of Distal-less homeobox 2 (Dlx-2) in regulating EMT and metabolic reprogramming during tumorigenesis.
  • To elucidate the molecular mechanisms by which Dlx-2, TGF-β, and Wnt signaling pathways interact to influence EMT, glycolytic switch, and mitochondrial function.

Main Methods:

  • Investigated the role of Dlx-2 in inducing EMT and glycolytic switch via Snail activation.
  • Examined the regulation of Dlx-2 by TGF-β and Wnt signaling pathways.
  • Analyzed the impact of TGF-β/Wnt and Dlx-2/Snail on cytochrome c oxidase (COX) expression and activity.
  • Identified specific COX subunits regulated by these pathways.

Main Results:

  • Dlx-2 directly induces EMT and glycolytic switch through Snail activation.
  • TGF-β and Wnt signaling pathways induce Dlx-2 and regulate EMT and glycolytic switch via Snail.
  • TGF-β/Wnt signaling suppresses mitochondrial respiration by downregulating cytochrome c oxidase (COX) in a Dlx-2/Snail-dependent manner.
  • COXVIc was identified as a common target of TGF-β, Wnt, Dlx-2, and Snail, playing a key role in TGF-β/Wnt-induced COX inhibition.

Conclusions:

  • Dlx-2 is a key mediator of TGF-β- and Wnt-induced EMT, glycolytic switch, and mitochondrial repression.
  • The Dlx-2/Snail axis is crucial for coordinating metabolic and migratory phenotypes in cancer cells.
  • Targeting the Dlx-2/Snail pathway may offer therapeutic strategies for inhibiting tumor progression.

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