The Significance of MMP-1 in EGFR-TKI-Resistant Lung Adenocarcinoma: Potential for Therapeutic Targeting

International Journal of Molecular Sciences
Ryoko SaitoHironobu Sasano

Abstract

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance is one of the most important problems in lung cancer therapy. Lung adenocarcinoma with EGFR-TKI resistance was reported to have higher abilities of invasion and migration than cancers sensitive to EGFR-TKI, but the function of matrix metalloproteinases (MMPs) has not been explored in EGFR-TKI-resistant lung adenocarcinoma. This study aims to clarify the significance of MMP-1 in EGFR-TKI-resistant lung adenocarcinoma. From the results of in vitro studies of migration and invasion assays using EGFR-TKI-sensitive and -resistant cell lines and phosphorylation antibody arrays using EGF and rapamycin, we first demonstrate that overexpression of MMP-1, which might follow activation of a mammalian target of rapamycin (mTOR) pathway, plays an important role in the migration and invasion abilities of EGFR-TKI-resistant lung adenocarcinoma. Additionally, immunohistochemical studies using 89 cases of lung adenocarcinoma demonstrate that high expression of MMP-1 is significantly correlated with poor prognosis and factors such as smoking history and the subtype of invasive mucinous adenocarcinoma. These are consistent with the results of this in vitro study. To ...Continue Reading

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Citations

Sep 14, 2019·International Journal of Molecular Sciences·Krista JuurikkaPirjo Åström
Aug 22, 2018·International Journal of Molecular Sciences·Misaki FueKiyoshi Ito
Jun 23, 2021·European Journal of Medicinal Chemistry·Sanjib DasTarun Jha
May 30, 2019·Pathology, Research and Practice·Shigehiro ItoHironobu Sasano

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Methods Mentioned

BETA
Feature Extraction
PCR
Assay
Antibody
antibody array

Software Mentioned

StatView
Feature Extraction
Genespring GX11
SPSS Statistics

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