DOI: 10.3390/biomedicines11092555">
 

Regulation of soluble E-cadherin signaling in non-small-cell lung cancer cells by nicotine, BDNF, and β-adrenergic receptor ligands

Document Type

Article

Publication Date

2023

Department/School

Chemistry

Publication Title

Biomedicines

Abstract

The ectodomain of the transmembrane protein E-cadherin can be cleaved and released in a soluble form referred to as soluble E-cadherin, or sE-cad, accounting for decreased E-cadherin levels at the cell surface. Among the proteases implicated in this cleavage are matrix metalloproteases (MMP), including MMP9. Opposite functions have been reported for full-length E-cadherin and sE-cad. In this study, we found increased MMP9 levels in the media of two non-small cell lung cancer (NSCLC) cell lines, A549 and H1299, treated with BDNF, nicotine, or epinephrine that were decreased upon cell treatment with the β-adrenergic receptor blocker propranolol. Increased MMP9 levels correlated with increased sE-cad levels in A549 cell media, and knockdown of MMP9 in A549 cells led to downregulation of sE-cad levels in the media. Previously, we reported that A549 and H1299 cell viability increased with nicotine and/or BDNF treatment and decreased upon treatment with propranolol. In investigating the function of sE-cad, we found that immunodepletion of sE-cad from the media of A549 cells untreated or treated with BDNF, nicotine, or epinephrine reduced activation of EGFR and IGF-1R, decreased PI3K and ERK1/2 activities, increased p53 activation, decreased cell viability, and increased apoptosis, while no effects were found using H1299 cells under all conditions tested.

Comments

J. Guthrie, D. Heyl, and H. G. Evans are faculty in EMU's Department of Chemistry.

*R. Ray, S. Goel, H. Al Khashali, B. Darweesh, B. Haddad, C. Wozniak, R. Ranzenberger, and J. Khalil are EMU students.

Link to Published Version

DOI: 10.3390/biomedicines11092555

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