Journal article
Regulation of epithelial-mesenchymal transition and metastasis by TGF-beta, P-bodies, and autophagy
Oncotarget, Vol.8(61), pp.103302-103314
11/28/2017
DOI: 10.18632/oncotarget.21871
PMCID: PMC5732729
PMID: 29262563
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-beta), 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-beta receptor, also promotes P-body formation. Removal of TGF-beta 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.
Details
- Title: Subtitle
- Regulation of epithelial-mesenchymal transition and metastasis by TGF-beta, P-bodies, and autophagy
- Creators
- Shana D. Hardy - Purdue University West LafayetteAparna Shinde - Purdue University West LafayetteWen-Horng Wang - Purdue University West LafayetteMichael K. Wendt - Purdue University West LafayetteRobert L. Geahlen - Purdue University West Lafayette
- Resource Type
- Journal article
- Publication Details
- Oncotarget, Vol.8(61), pp.103302-103314
- DOI
- 10.18632/oncotarget.21871
- PMID
- 29262563
- PMCID
- PMC5732729
- NLM abbreviation
- Oncotarget
- ISSN
- 1949-2553
- eISSN
- 1949-2553
- Publisher
- Impact Journals Llc
- Number of pages
- 13
- Grant note
- R01AI098132 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) AI098132; CA207751 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01CA207751 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 11/28/2017
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984459633402771
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