@Article{096504018X15426271404407,
AUTHOR = {Xinwen Wang, Fupeng Zhang, Xi Yang, Meiping Xue, Xiaoli Li, Yu Gao, Likun Liu},
TITLE = {Secreted Phosphoprotein 1 (SPP1) Contributes to Second-Generation EGFR  Tyrosine Kinase Inhibitor Resistance in Non-Small Cell Lung Cancer},
JOURNAL = {Oncology Research},
VOLUME = {27},
YEAR = {2019},
NUMBER = {8},
PAGES = {871--877},
URL = {http://www.techscience.com/or/v27n8/48616},
ISSN = {1555-3906},
ABSTRACT = {Second-generation irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), 
afatinib, has been approved for treating <i>EGFR</i> mutant lung cancer patients, but the mechanism of acquired 
resistance to afatinib has not been well studied. In this study, we established afatinib acquired resistant cell 
lines. Gene array technology was used to screen changes in gene expression between afatinib-resistant lung 
cancer cells and parental cells. Our results showed that secreted phosphoprotein 1 (SPP1) was significantly 
increased in afatinib-resistant lung cancer cells. To study the effect of SPP1 on afatinib resistance, siSPP1 was 
used to knock down SSP1 in afatinib-resistant lung cancer cells. Then sensitivity to afatinib and invasive ability were studied. We found that knockdown of SPP1 increased sensitivity of lung cancer cells to afatinib and 
decrease the ability of invasion. Of clinical significance, we found that SSP1 was upregulated in lung cancer 
tissues compared with adjacent normal tissues, and low level of SSP1 was strongly associated with better 
overall survival. Our results suggest that SPP1 enhanced the second-generation EGFR TKI resistance in lung 
cancer, and inhibiting SPP1 might be a therapeutic target to overcome afatinib resistance.},
DOI = {10.3727/096504018X15426271404407}
}