YAP Promotes Malignant Progression of <i>Lkb1</i>-Deficient Lung Adenocarcinoma through Downstream Regulation of Survivin

Zhang, Wenjing; Gao, Yijun; Li, Fuming; Tong, Xinyuan; Ren, Yan; Han, Xiuxin; Yao, Shun; Long, Fei; Yang, Zhongzhou; Fan, Heng‐Yu; Zhang, Lei; Ji, Hongbin

doi:10.1158/0008-5472.can-14-3396

Cited by 85 publications

(70 citation statements)

References 36 publications

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“…(14,15,18,21) As a possible mechanism for survivin expression in angiosarcoma, we assumed YAP nuclear translocation, namely, Hippo pathway inactivation, because survivin is one of the YAP target genes. (14,39,40) Interestingly, our findings indicate that YAP is specifically expressed and translocated in the nucleus in angiosarcomas; namely, Hippo pathway inactivation (Hippo-OFF). However, the Hippo pathway activation modes were not related to angiosarcoma patient survival.…”

Section: Discussionmentioning

confidence: 71%

“…YAP is one of the core components of the Hippo pathway and nuclear YAP localization indicates Hippo pathway inactivation . As a possible mechanism for survivin expression in angiosarcoma, we assumed YAP nuclear translocation, namely, Hippo pathway inactivation, because survivin is one of the YAP target genes . Interestingly, our findings indicate that YAP is specifically expressed and translocated in the nucleus in angiosarcomas; namely, Hippo pathway inactivation (Hippo‐OFF).…”

Section: Discussionmentioning

confidence: 76%

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Survivin: A novel marker and potential therapeutic target for human angiosarcoma

et al. 2017

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Human angiosarcoma is a rare malignant vascular tumor associated with extremely poor clinical outcome and generally arising in skin of the head and neck region. However, little is known about the molecular pathogeneses and useful immunohistochemical markers of angiosarcoma. To investigate the mechanisms of angiosarcoma progression, we collected 85 cases of human angiosarcoma specimens with clinical records and analyzed ISO‐HAS‐B patient‐derived angiosarcoma cells. As control subjects, 54 cases of hemangioma and 34 of pyogenic granuloma were collected. Remarkably, consistent with our recent observations regarding the involvement of survivin expression following Hippo pathway inactivation in the neoplastic proliferation of murine hemangioendothelioma cells and human infantile hemangioma, nuclear survivin expression was observed in all cases of angiosarcoma but not in hemangiomas and pyogenic granulomas, and the Hippo pathway was inactivated in 90.3% of yes‐associated protein (YAP) ‐positive angiosarcoma cases. However, survivin expression modes and YAP localization (Hippo pathway activation modes) were not correlated with survival. In addition, we confirmed that survivin small interference RNA (siRNA) transfection and YM155, an anti‐survivin drug, elicited decreased nuclear survivin expression and cell proliferation in ISO‐HAS‐B cells which expressed survivin consistently. Conclusively, these findings support the importance of survivin as a good marker and critical regulator of cellular proliferation for human angiosarcoma and YM155 as a potential therapeutic agent.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 76%

Survivin: A novel marker and potential therapeutic target for human angiosarcoma

et al. 2017

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“…In these tumor cells, YAP can not be phosphorylated and degraded effectively. Unphosphorylated YAP enters into the nucleus where YAP binds and activates transcription factors, altering the expression of genes involved in cell proliferation and apoptosis [21–23]. In addition, YAP has been identified as an oncoprotein elevated in cholangiocarcinoma [24], ovarian cancer [25], colorectal cancer [26], hepatocellular carcinoma [27] and gastric cancer [28].…”

Section: Introductionmentioning

confidence: 99%

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

Huang

Gao

et al. 2016

J Exp Clin Cancer Res

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BackgroundYes-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.MethodsThe 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.ResultsYAP 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.ConclusionOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0414-z) contains supplementary material, which is available to authorized users.

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“…It has been shown that apoptotic cells induce fibrogenesis (43) and activate YAP to resist apoptotic progression (44). Thus, we studied apoptosis in the liver tissue of WT and LKO mice.…”

Section: Resultsmentioning

confidence: 99%

TAZ stimulates liver regeneration through interleukin‐6–induced hepatocyte proliferation and inhibition of cell death after liver injury

Kim

Park

et al. 2019

The FASEB Journal

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In response to liver injury, the liver undergoes a regeneration process to retain its mass and function. However, the regeneration mechanism has not been fully clarified. This study investigated the role of transcriptional coactivator with PDZ‐binding motif (TAZ), a Hippo‐signaling effector, in liver regeneration. We observed that TAZ stimulates liver regeneration after liver injury. After partial hepatectomy (PHx) or carbon tetrachloride damage, TAZ was required for liver regeneration to increase hepatic cell proliferation and resist hepatic apoptosis, which were decreased in liver‐specific TAZ knockout (LKO) mice. TAZ stimulated macrophage infiltration, resulting in IL‐6 production, which induced liver regeneration. In LKO mice, IL‐6–induced activation of signal transducer and activator of transcription 3, ERK, and PKB was decreased. We also observed that periductal fibrogenesis was significantly increased in LKO mice during liver regeneration after PHx, which was caused by increased hepatic apoptosis. Our results suggest that TAZ stimulates liver regeneration through IL‐6–induced hepatocyte proliferation and inhibition of cell death after liver injury.—Kim, A. R., Park, J. I., Oh, H. T., Kim, K. M., Hwang, J.‐H., Jeong, M. G., Kim, E.‐H., Hwang, E. S., Hong, J.‐H. TAZ stimulates liver regeneration through interleukin‐6–induced hepatocyte proliferation and inhibition of cell death after liver injury. FASEB J. 33, 5914–5923 (2019). http://www.fasebj.org

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YAP Promotes Malignant Progression of Lkb1-Deficient Lung Adenocarcinoma through Downstream Regulation of Survivin

Cited by 85 publications

References 36 publications

Survivin: A novel marker and potential therapeutic target for human angiosarcoma

Survivin: A novel marker and potential therapeutic target for human angiosarcoma

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

TAZ stimulates liver regeneration through interleukin‐6–induced hepatocyte proliferation and inhibition of cell death after liver injury

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