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Knockdown of BAG3 induces epithelial-mesenchymal transition in thyroid cancer cells through ZEB1 activation

X Meng1, D-H Kong2, N Li2

  • 11] Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001, China [2] Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, China.

Cell Death & Disease
|March 1, 2014
PubMed

Insights

Bcl-2-associated athanogene 3 (BAG3) regulates epithelial-mesenchymal transition (EMT) in thyroid cancer. BAG3 knockdown promotes cancer cell invasion and metastasis by activating ZEB1, offering potential therapeutic targets.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Epithelial-mesenchymal transition (EMT) is crucial for carcinoma invasion and metastasis.
  • ZEB1, a transcription factor, drives EMT by suppressing E-cadherin expression.
  • Bcl-2-associated athanogene 3 (BAG3) has diverse cellular roles, with its involvement in EMT recently noted but mechanistically unclear.

Purpose of the Study:

  • To elucidate the role and underlying mechanisms of BAG3 in epithelial-mesenchymal transition (EMT) and metastasis in thyroid cancer cells.
  • To investigate how BAG3 influences ZEB1 expression and subsequent cellular behaviors.

Main Methods:

  • Thyroid cancer cell lines were used to study EMT.
  • BAG3 was knocked down to observe its effects on cellular phenotypes.
  • ZEB1 transcriptional activation and nuclear accumulation of β-catenin were analyzed.

Main Results:

  • Knockdown of BAG3 induced EMT and increased cell migration and invasion in thyroid cancer cells.
  • BAG3 knockdown led to the transcriptional activation of ZEB1.
  • Nuclear accumulation of β-catenin was observed following BAG3 knockdown, mediating ZEB1 activation.

Conclusions:

  • BAG3 acts as a suppressor of ZEB1 expression in thyroid cancer cells, thereby inhibiting EMT and metastasis.
  • BAG3 is a key regulator of ZEB1-mediated EMT and metastasis, representing a potential therapeutic target for thyroid cancer.
  • Targeting BAG3 could offer a novel strategy to prevent or treat thyroid cancer invasion and metastasis.

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