Oncotarget

Research Papers:

Regulation of epithelial-mesenchymal transition and metastasis by TGF-β, P-bodies, and autophagy

Shana D. Hardy, Aparna Shinde, Wen-Horng Wang, Michael K. Wendt, Robert L. Geahlen _

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Oncotarget. 2017; 8:103302-103314. https://doi.org/10.18632/oncotarget.21871

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Abstract

Shana D. Hardy1, Aparna Shinde1, Wen-Horng Wang1, Michael K. Wendt1 and Robert L. Geahlen1

1Department of Medicinal Chemistry and Molecular Pharmacology, and the Purdue Center for Cancer Research, Purdue University, West Lafayette, IN, 47907, USA

Correspondence to:

Robert L. Geahlen, email: geahlen@purdue.edu

Michael K. Wendt, email: mwendt@purdue.edu

Keywords: P-body, autophagy, transforming growth factor beta (TGF-β), epithelial-mesenchymal transition (EMT), metastasis

Received: August 24, 2017     Accepted: September 29, 2017     Published: October 17, 2017

ABSTRACT

Processing bodies (P-bodies) are ribonucleoprotein complexes involved in post-transcriptional mRNA metabolism that accumulate in cells exposed to various stress stimuli. The treatment of mammary epithelial cells with transforming growth factor-beta (TGF-β), triggers epithelial-mesenchymal transition (EMT), and induces the formation of P-bodies. Ectopic expression of the transcription factor TWIST, which stimulates EMT downstream of the TGF-β receptor, also promotes P-body formation. Removal of TGF-β from treated cells results in the clearance of P-bodies by a process that is blocked by inhibitors of autophagy. Activators of autophagy enhance P-body clearance and block EMT. Blockage of P-body formation by disruption of the gene for DDX6, a protein essential for P-body assembly, blocks EMT and prevents tumor cell metastasis in vivo. These studies suggest critical roles for P-body formation and autophagy in transitions of cancer cells between epithelial and mesenchymal phenotypes and help explain how autophagy functions to promote or suppress tumor cell growth during different stages of tumorigenesis.

Author Information

Shana D. Hardy

Aparna Shinde

Wen-Horng Wang

Michael K. Wendt

Robert L. Geahlen
Primary Contact  _


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