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Inhibition of YAP suppresses CML cell proliferation and enhances efficacy of imatinib in vitro and in vivo.

Abstract：

BACKGROUND:Yes-associated protein (YAP), an essential component of Hippo pathway, was identified as an oncoprotein which participated in the progression of various malignancies. However, its role in chronic myeloid leukemia (CML) remains to be further clarified. METHODS:The expression of YAP in CML cells was determined by western blotting. Next, the effects of YAP knockdown and YAP inhibitor on CML cells were evaluated by MTT assay, flow cytometry (FCM) and Wright's staining. Moreover, K562 induced mice model was employed to further investigate the role of YAP in vivo. RESULTS:YAP was overexpressed in CML cells. Knockdown of YAP by si-RNA or inhibition the function of YAP using verteporfin (VP) not only inhibited the proliferation, induced the apoptosis of CML cells but also reduced the expression of YAP target genes c-myc and survivin. Additionally, VP enhanced the efficacy of imatinib (IM) in vitro and suppressed leukemogenesis in vivo. CONCLUSION:Our results indicate that YAP may play an important role in the proliferation and leukemogenesis of CML cells. Genetic or pharmacological inhibition of YAP provides a novel treatment strategy for CML.

journal_name

J Exp Clin Cancer Res

journal_title

Journal of experimental & clinical cancer research : CR

authors

Li H,Huang Z,Gao M,Huang N,Luo Z,Shen H,Wang X,Wang T,Hu J,Feng W

doi

10.1186/s13046-016-0414-z

subject

Has Abstract

pub_date

2016-09-06 00:00:00

pages

134

issue

1

eissn

0392-9078

issn

1756-9966

pii

10.1186/s13046-016-0414-z

journal_volume

35

pub_type

杂志文章

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