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Verkoeijen et al. J Cancer Metastasis Treat 2019;5:51 Journal of Cancer
DOI: 10.20517/2394-4722.2019.06 Metastasis and Treatment

Original Article Open Access

Paxillin serine 178 phosphorylation in control of
cell migration and metastasis formation through

regulation of EGFR expression in breast cancer

Saertje Verkoeijen , Ya-Feng Ma , Wies van Roosmalen , Reshma Lalai , Martine H. A. M. van Miltenburg ,
2
2
1
2
2
Marjo de Graauw , Bob van de Water , Sylvia E. Le Dévédec 2
2
2
1 Institute for Life Sciences & Chemistry, Hogeschool Utrecht HU, Utrecht 3501 AA, the Netherlands.
2 Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University, Leiden 2300 RA, the
Netherlands.
Correspondence to: Dr. Sylvia E. Le Dévédec, Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research,
Leiden, 2300 RA, Netherlands. E-mail: s.e.ledevedec@lacdr.leidenuniv.nl
How to cite this article: Verkoeijen S, Ma YF, van Roosmalen W, Lalai R, van Miltenburg MHAM, de Graauw M, van de Water B,
Le Dévédec SE. Paxillin serine 178 phosphorylation in control of cell migration and metastasis formation through regulation of
EGFR expression in breast cancer. J Cancer Metastasis Treat 2019;5:51. http://dx.doi.org/10.20517/2394-4722.2019.06
Received: 9 Jan 2019 First Decision: 9 Feb 2019 Revised: 24 Apr 2019 Accepted: 7 May 2019 Published: 21 Jun 2019

Science Editor: William Schiemann Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract

Aim: Paxillin is a well-known multidomain scaffold protein that is involved in the regulation of cell-matrix adhesion
dynamics, a process required for the tumor cell migration and invasion. Phosphorylation of the serine residue 178
requires c-Jun NH2-terminal kinase (JNK) activation, which occurs downstream of epidermal growth factor receptor
(EGFR)-mediated signaling and drives cell migration. In this study, we investigated the significance of paxillin Ser178
phosphorylation in breast cancer progression.

Methods: We employed the rat mammary carcinoma MTLn3 cell line with which we established stabile variants of
both wild type and mutant GFP-paxillin constructs. With those, we next performed several in vitro assays including
cell proliferation, migration and focal adhesion dynamics. Finally, we monitored the metastatic spread of both cell
line variants in an othrotopic mouse model for breast cancer.

Results: Here we show that expression of the phospho-defective mutant paxillinS178A in the metastatic mammary
adenocarcinoma MTLn3 cell-line significantly decreased EGF-induced cell migration, which was correlated with
impaired focal adhesion dynamics. Moreover, paxillinS178A attenuated lung metastasis formation in an orthotopic
in vivo mammary gland tumor/metastasis model, demonstrating the importance of JNK-mediated paxillin
phosphorylation in breast cancer progression. Expression of paxillinS178A caused a decrease in EGFR expression,

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
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