@article{c68083ad8a81415f92f9e9cf69608b63,
title = "Lapatinib inhibits CIP2A/PP2A/p-Akt signaling and induces apoptosis in triple negative breast cancer cells",
abstract = "We tested the efficacy of lapatinib, a dual tyrosine kinase inhibitor which interrupts the HER2 and epidermal growth factor receptor (EGFR) pathways, in a panel of triple-negative breast cancer (TNBC) cells, and examined the drug mechanism. Lapatinib showed an anti-proliferative effect in HCC 1937, MDA-MB-468, and MDA-MB-231 cell lines. Lapatinib induced significant apoptosis and inhibited CIP2A and p-Akt in a dose and time-dependent manner in the three TNBC cell lines. Overexpression of CIP2A reduced lapatinib-induced apoptosis in MDA-MB-468 cells. In addition, lapatinib increased PP2A activity (in relation to CIP2A inhibition). Moreover, lapatinib-induced apoptosis and p-Akt downregulation was attenuated by PP2A antagonist okadaic acid. Furthermore, lapatinib indirectly decreased CIP2A transcription by disturbing the binding of Elk1 to the CIP2A promoter. Importantly, lapatinib showed anti-tumor activity in mice bearing MDA-MB-468 xenograft tumors, and suppressed CIP2A as well as p-Akt in these xenografted tumors. In summary, inhibition of CIP2A determines the effects of lapatinib-induced apoptosis in TNBC cells. In addition to being a dual tyrosine kinase inhibitor of HER2 and EGFR, lapatinib also inhibits CIP2A/PP2A/p-Akt signaling in TNBC cells.",
keywords = "Apoptosis, CIP2A, Lapatinib, PP2A, Triple-negative breast cancer",
author = "Liu, {Chun Yu} and Hu, {Ming Hung} and Hsu, {Chia Jung} and Huang, {Chun Teng} and Wang, {Duen Shian} and Tsai, {Wen Chun} and Chen, {Yi Ting} and Lee, {Chia Han} and Chu, {Pei Yi} and Hsu, {Chia Chi} and Chen, {Ming Huang} and Shiau, {Chung Wai} and Tseng, {Ling Ming} and Chen, {Kuen Feng}",
note = "Funding Information: This research was supported by grants from the Taiwan Clinical Oncology Research Foundation and from the Yen Tjing Ling Medical Foundation (CI-104-07); the Ministry of Science and Technology, Taiwan (MOST 103-2325-B-075-002, MOST 102-2325-B-075-003); Yang-Ming Branch of Taipei City Hospital (104 No.35, M-1A00-B-B17-35); Taipei Veterans General Hospital (V103C-141, V104C-151, V105C-067); TVGH-NTUH Joint Research Program (VN103-08) from Taipei Veterans General Hospital and National Taiwan-University Hospital and the Ministry of Health and Welfare, Executive Yuan, Taiwan (MOHW104-TD-B-111-02 for the Center of Excellence for Cancer Research at Taipei Veterans General, and MOHW103TDU-212-114002). This study is also partially supported by the Chong Hin Loon Memorial Cancer and the Biotherapy Research Center of National Yang-Ming University, Taipei, Taiwan.",
year = "2016",
doi = "10.18632/oncotarget.7035",
language = "English",
volume = "7",
pages = "9135--9149",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "8",
}