Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/103566
Title: Overexpression of GRB2 enhances epithelial to mesenchymal transition of A549 cells by upregulating SNAIL expression
Authors: Mitra, Payal
Kalailingam, Pazhanichamy
Thanabalu, Thirumaran
Tan, Hui Bing
Keywords: E-cadherin
Cell Adhesion
DRNTU::Science::Biological sciences
Issue Date: 2018
Source: Mitra, P., Kalailingam, P., Tan, H. B., & Thanabalu, T. (2018). Overexpression of GRB2 enhances epithelial to mesenchymal transition of A549 cells by upregulating SNAIL expression. Cells, 7(8), 97-. doi:10.3390/cells7080097
Series/Report no.: Cells
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.
URI: https://hdl.handle.net/10356/103566
http://hdl.handle.net/10220/47362
ISSN: 2073-4409
DOI: 10.3390/cells7080097
Rights: © 2018 The Author(s). Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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