Chang, Yoojin Park, Kyong Hwa Lee, Ji Eun Han, Ki-Cheol 2024-01-19T21:32:42Z 2024-01-19T21:32:42Z 2021-09-04 2018-10-20 0006-291X https://pubs.kist.re.kr/handle/201004/120780 The human epidermal growth factor receptor 2 (HER2)-positive breast cancer with overexpression of HER2 accounts for approximately 25% of breast cancers and is more aggressive than other types of breast cancer. Lapatinib has been widely used as a HER2-targeted therapy, however, a number of patients develop lapatinib resistance and still suffer from poor prognosis. Therefore, it is essential to identify novel therapeutic targets that could overcome lapatinib resistance. In this study, we carried out phosphoproteomic analysis of lapatinib sensitive and resistant cell lines (SKBR3 and SKBR3-LR) using stable isotope labeling with amino acids in cell culture (SILAC). We identified 3808 phosphopeptides from 1807 proteins and then analyzed signaling pathways, Gene Ontology, and protein-protein interaction networks. Finally, we identified PAK2 as a therapeutic target from the network analysis and validated that PAK2 knockdown and PAK inhibitor treatment resensitize the lapatinib resistant cells to lapatinib. This results suggest that PAK2 is a potent therapeutic target to overcome acquired lapatinib resistance in HER2-positive breast cancer cells. (C) 2018 Elsevier Inc. All rights reserved. English ACADEMIC PRESS INC ELSEVIER SCIENCE TYROSINE KINASE INHIBITION EXPRESSION ACTIVATION GENE PHOSPHORYLATION TRANSFORMATION AMPLIFICATION APOPTOSIS STRATEGY Phosphoproteomic analysis reveals PAK2 as a therapeutic target for lapatinib resistance in HER2-positive breast cancer cells Article 10.1016/j.bbrc.2018.09.086 1 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.505, no.1, pp.187 - 193 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 505 1 187 193 scie scopus 000447815300030 2-s2.0-85053666739 Biochemistry & Molecular Biology Biophysics Biochemistry & Molecular Biology Biophysics Article TYROSINE KINASE INHIBITION EXPRESSION ACTIVATION GENE PHOSPHORYLATION TRANSFORMATION AMPLIFICATION APOPTOSIS STRATEGY HER2-Positive breast cancer Lapatinib resistance Phosphoproteomics PAK2