Open Access
ARTICLE
Secreted Phosphoprotein 1 (SPP1) Contributes to Second-Generation EGFR Tyrosine Kinase Inhibitor Resistance in Non-Small Cell Lung Cancer
Xinwen Wang, Fupeng Zhang, Xi Yang, Meiping Xue, Xiaoli Li, Yu Gao, Likun Liu
Department of Oncology, Shanxi Province Hospital of Traditional Chinese Medicine, Taiyuan, P.R. China
Oncology Research 2019, 27(8), 871-877. https://doi.org/10.3727/096504018X15426271404407
Abstract
Second-generation irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI),
afatinib, has been approved for treating
EGFR 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.
Keywords
Cite This Article
Wang, X., Zhang, F., Yang, X., Xue, M., Li, X. et al. (2019). Secreted Phosphoprotein 1 (SPP1) Contributes to Second-Generation EGFR Tyrosine Kinase Inhibitor Resistance in Non-Small Cell Lung Cancer.
Oncology Research, 27(8), 871–877.