| RRC ID |
55763
|
| 著者 |
Saito R, Miki Y, Ishida N, Inoue C, Kobayashi M, Hata S, Yamada-Okabe H, Okada Y, Sasano H.
|
| タイトル |
The Significance of MMP-1 in EGFR-TKI-Resistant Lung Adenocarcinoma: Potential for Therapeutic Targeting.
|
| ジャーナル |
Int J Mol Sci
|
| 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 conclude, this study provides insights into the development of a possible alternative therapy manipulating MMP-1 and the mTOR signaling pathway in EGFR-TKI-resistant lung adenocarcinoma.
|
| 巻・号 |
19(2)
|
| 公開日 |
2018-2-18
|
| DOI |
10.3390/ijms19020609
|
| PII |
ijms19020609
|
| PMID |
29463039
|
| PMC |
PMC5855831
|
| MeSH |
Adenocarcinoma / drug therapy*
Adenocarcinoma / enzymology*
Adenocarcinoma / pathology
Adenocarcinoma of Lung
Aged
Cell Line, Tumor
Cell Movement / genetics
Drug Resistance, Neoplasm* / genetics
ErbB Receptors / antagonists & inhibitors*
ErbB Receptors / metabolism
Female
Gene Expression Regulation, Neoplastic / drug effects
Humans
Lung Neoplasms / drug therapy*
Lung Neoplasms / enzymology*
Lung Neoplasms / pathology
Male
Matrix Metalloproteinase 1 / genetics
Matrix Metalloproteinase 1 / metabolism*
Molecular Targeted Therapy*
Multivariate Analysis
Neoplasm Invasiveness
Protein Kinase Inhibitors / pharmacology
Protein Kinase Inhibitors / therapeutic use*
RNA, Messenger / genetics
RNA, Messenger / metabolism
Signal Transduction
TOR Serine-Threonine Kinases / metabolism
|
| IF |
4.183
|
| 引用数 |
7
|
| リソース情報 |
| ヒト・動物細胞 |
PC-9(RCB4455) |
