Journal article
EMT Transition Alters Interstitial Fluid Flow-Induced Signaling in ERBB2-Positive Breast Cancer Cells
Molecular cancer research, v 13(4), pp 755-764
01 Apr 2015
PMID: 25566992
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
A variety of biophysical forces are altered in the tumor microenvironment (TME) and these forces can influence cancer progression. One such force is interstitial fluid flow (IFF)-the movement of fluid through the tissue matrix. IFF was previously shown to induce invasion of cancer cells, but the activated signaling cascades remain poorly understood. Here, it is demonstrated that IFF induces invasion of ERBB2/HER2-expressing breast cancer cells via activation of phosphoinositide-3-kinase (PI3K). In constitutively activate ERBB2-expressing cells that have undergone epithelial-to-mesenchymal transition (EMT), IFF-mediated invasion requires the chemokine receptor CXCR4, a gradient of its ligand CXCL12, and activity of the PI3K catalytic subunits p110 alpha and beta. In wild-type ERBB2-expressing cells, IFF-mediated invasion is chemokine receptor-independent and requires only p110 alpha activation. To test whether cells undergoing EMT alter their signaling response to IFF, TGF beta 1 was used to induce EMT in wild-type ERBB2-expressing cells, resulting in IFF-induced invasion dependent on CXCR4 and p110 beta.
Implications: This study identifies a novel signaling mechanism for interstitial flow-induced invasion of ERBB2-expressing breast cancer cells, one that depends on EMT and acts through a CXCR4-PI3K pathway. These findings suggest that the response of cancer cells to interstitial flow depends on EMT status and malignancy.
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Details
- Title
- EMT Transition Alters Interstitial Fluid Flow-Induced Signaling in ERBB2-Positive Breast Cancer Cells
- Creators
- Alimatou M. Tchafa - Drexel UniversityMi Ta - Drexel UniversityMauricio J. Reginato - Drexel UniversityAdrian C. Shieh - Drexel University
- Publication Details
- Molecular cancer research, v 13(4), pp 755-764
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 10
- Grant note
- Pennsylvania Department of Health CURE grant from Drexel University College of Medicine
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000354812000016
- Scopus ID
- 2-s2.0-84928005686
- Other Identifier
- 991019169118604721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Cell Biology
- Oncology