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



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.



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.



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.
Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, Chongqing Medical University, No.1, Yixueyuan Road, Chongqing, 400016, China.
Hui
H
Li
Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, Chongqing Medical University, No.1, Yixueyuan Road, Chongqing, 400016, China.
Zhenglan
Z
Huang
Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, Chongqing Medical University, No.1, Yixueyuan Road, Chongqing, 400016, China.
Miao
M
Gao
Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, Chongqing Medical University, No.1, Yixueyuan Road, Chongqing, 400016, China.
Ningshu
N
Huang
Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, Chongqing Medical University, No.1, Yixueyuan Road, Chongqing, 400016, China.
Zhenhong
Z
Luo
Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, Chongqing Medical University, No.1, Yixueyuan Road, Chongqing, 400016, China.
Huawei
H
Shen
Department of Hematology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China.
Xin
X
Wang
Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, Chongqing Medical University, No.1, Yixueyuan Road, Chongqing, 400016, China.
Teng
T
Wang
Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, Chongqing Medical University, No.1, Yixueyuan Road, Chongqing, 400016, China.
Jing
J
Hu
Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, Chongqing Medical University, No.1, Yixueyuan Road, Chongqing, 400016, China. fengwlcqmu@sina.com.
Wenli
W
Feng
D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D018922:HL-60 Cells; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage* / Q000494:pharmacology; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D010750:Phosphoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011166:Porphyrins / Q000008:administration & dosage* / Q000494:pharmacology; D014157:Transcription Factors; D015854:Up-Regulation / Q000187:drug effects; D000077362:Verteporfin; D023041:Xenograft Model Antitumor Assays; D000091102:YAP-Signaling Proteins
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D010750:Phosphoproteins; D011166:Porphyrins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D000077362:Verteporfin; D000068877:Imatinib Mesylate
Bcr/Abl; Chronic myeloid leukemia; IM; Leukemogenesis; Verteporfin; YAP