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Cells 2018, 7(8), 97; https://doi.org/10.3390/cells7080097

Overexpression of GRB2 Enhances Epithelial to Mesenchymal Transition of A549 Cells by Upregulating SNAIL Expression

1
Department of Molecular Medicine, STRF, University of Texas Health San Antonio, 8403 Floyd Curl Dr, San Antonio, TX 78229, USA
2
School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore
3
National University Health System (NUHS), 119228 Singapore, Singapore
*
Author to whom correspondence should be addressed.
Received: 19 June 2018 / Revised: 28 July 2018 / Accepted: 1 August 2018 / Published: 7 August 2018
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Abstract

GRB2 is an adaptor protein which interacts with phosphorylated TGF-β receptor and is critical for mammary tumour growth. We found that TGF-β1-induced EMT increased GRB2 expression in A549 cells (non-small cell lung cancer). Overexpression of GRB2 (A549GRB2) enhanced cell invasion while knocking down GRB2 (A549GRB2KD) reduced cell migration and invasion, probably due to increased vinculin and reduced Paxillin patches in A549GRB2KD cell. TGF-β1-induced EMT was more pronounced in A549GRB2 cells and attenuated in A549GRB2KD cells. This could be due to the reduced expression of E-cadherin in A549GRB2 and increased expression of E-cadherin in A549GRB2KD cells, even before TGF-β1 stimulation. Expression of SNAIL was elevated in A549GRB2 cells and was further enhanced by TGF-β1 stimulation, suggesting that GRB2 down-regulates E-cadherin by enhancing the expression of SNAIL. The N-SH3 domain of GRB2 was critical for suppressing E-cadherin expression, while the C-SH3 domain of GRB2 mediating interaction with proteins such as N-WASP was critical for promoting invasion, and the SH2 domain was critical for suppressing E-cadherin expression and invasion. Thus, our data suggests that GRB2 enhances EMT by suppressing E-cadherin expression and promoting invasion probably through N-WASP to promote metastasis. View Full-Text
Keywords: E-cadherin; cell adhesion; migration; actin cytoskeleton E-cadherin; cell adhesion; migration; actin cytoskeleton
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Mitra, P.; Kalailingam, P.; Tan, H.B.; Thanabalu, T. Overexpression of GRB2 Enhances Epithelial to Mesenchymal Transition of A549 Cells by Upregulating SNAIL Expression. Cells 2018, 7, 97.

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