Premium
Differential regulation of cellular signaling pathways that control cellular migration in human lung cancer cell lines: The effects of lysophosphatidic acid, urokinase‐type plasminogen activator, and phenylephrine
Author(s) -
Canine Jenny,
Kutz Craig,
Rastedt Danielle,
Heinz Blake,
Taves Jennifer,
Provost Joseph,
Wallert Mark
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a295-a
Subject(s) - lysophosphatidic acid , mapk/erk pathway , microbiology and biotechnology , cell migration , cancer research , chemistry , cancer cell , cell growth , stress fiber , plasminogen activator , signal transduction , cell , biology , endocrinology , focal adhesion , cancer , medicine , biochemistry , receptor
Lung cancer is the leading cause of cancer deaths in the U.S. but the prognosis for many lung cancer types remains poor. In this study, our goal was to translate our growing understanding of the regulation of cell migration in lung fibroblasts to human lung cancer metastasis. In CCL39 fibroblasts, several agonists increase cell motility by increasing phospholipase D (PLD) activation, ERK phosphorylation, stress fiber formation, and MMP9 activation. Thus we screened cellular responses to lysophosphatidic acid (LPA), urokinase plasminogen activator (uPA) and phenylephrine (PE) in the human lung cancer cell lines, H460, H358, H69AR, and A549. Basel phospho‐ERK levels were high among all four cell types. PE, LPA, and uPA addition decreased ERK phosphorylation in H460 and H358 cells. The decrease in ERK activation induced by LPA and uPA could be blocked by the use of primary butanol to disrupt PLD signaling. The PE decrease in ERK activation was not altered by butanol. In H358 cells, PE, LPA, and uPA addition decreased PLD activity while in H460 cells PE decreased and LPA increased PLD activity. In H460 cells PE, LPA, and uPA all increased stress fiber formation. NIH 1 R15 HL074924 ‐01A1