R331W Missense Mutation of Oncogene <i>YAP1</i> Is a Germline Risk Allele for Lung Adenocarcinoma With Medical Actionability

Chen, Hsuan Yu; Yu, Sung-Liang; Ho, Bing-Ching; Su, Kang-Yi; Hsu, Yi Chiung; Chang, Chi Chen; Li, Yu Cheng; Yang, Shan; Hsu, Pin Yen; Ho, Hao; Chang, Yun‐chien; Chen, Chih Yi; Yang, Hwai I.; Hsu, Chiao Po; Yang, Tsung Ying; Chen, Kun Chieh; Hsu, Kuo-Hsuan; Tseng, Jeng‐Sen; Hsia, Jiun-Yi; Chuang, Chun‐Yi; Yuan, Shinsheng; Lee, Hsuan-Shu; Liu, Chia-Hsin; Wu, Guan I.; Hsiung, Chao A.; Chen, Yuh Min; Wang, Chih Liang; Huang, Ming Shyan; Yu, Chong Jen; Chen, Kuan‐Yu; Tsai, Ying Huang; Su, Wu Chou; Chen, Huei‐Wen; Chen, Jeremy J.W.; Chen, Chien Jen; Chang, Gee Chen; Yang, Pan Chyr; Li, Ker Chau

doi:10.1200/jco.2014.59.3590

Cited by 86 publications

(67 citation statements)

References 40 publications

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“…Concordantly, YAP and TAZ have been considered as therapeutic targets for a number of cancers (Liu-Chittenden et al 2012;Jiao et al 2014;Yu et al 2014;Zhou et al 2015b) as well as several other diseases . Notably, the R331W missense mutation of YAP has recently been linked to a germline risk in lung adenocarcinoma (Chen et al 2015a). Moreover, almost all epithelioid hemangioendotheliomas contain gene fusions of TAZ-CAMTA1, TAZ-FOSB, or YAP-TFE3 (Tanas et al 2011;Antonescu et al 2013;Patel et al 2015), strongly supporting a role of YAP/TAZ in human tumorigenesis.…”

Section: The Yap/taz Transcriptional Programs and Their Functional Oumentioning

confidence: 92%

Mechanisms of Hippo pathway regulation

2016

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The Hippo pathway was initially identified in Drosophila melanogaster screens for tissue growth two decades ago and has been a subject extensively studied in both Drosophila and mammals in the last several years. The core of the Hippo pathway consists of a kinase cascade, transcription coactivators, and DNA-binding partners. Recent studies have expanded the Hippo pathway as a complex signaling network with >30 components. This pathway is regulated by intrinsic cell machineries, such as cell–cell contact, cell polarity, and actin cytoskeleton, as well as a wide range of signals, including cellular energy status, mechanical cues, and hormonal signals that act through G-protein-coupled receptors. The major functions of the Hippo pathway have been defined to restrict tissue growth in adults and modulate cell proliferation, differentiation, and migration in developing organs. Furthermore, dysregulation of the Hippo pathway leads to aberrant cell growth and neoplasia. In this review, we focus on recent developments in our understanding of the molecular actions of the core Hippo kinase cascade and discuss key open questions in the regulation and function of the Hippo pathway.

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Section: The Yap/taz Transcriptional Programs and Their Functional Oumentioning

confidence: 92%

Mechanisms of Hippo pathway regulation

2016

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“…In lung cancer, knockdown of YAP and TAZ reduced cell migration and transplantation of metastatic disease in vivo [21,23]. Also, a missense mutation in the YAP1 gene appears to increase the risk for lung adenocarcinoma [29]. Our group has shown the contribution of the Hippo pathway to cancer cell/ endothelial crosstalk and vascular invasion.…”

Section: The Hippo Pathway and Cancermentioning

confidence: 91%

Cell Density Regulates Cancer Metastasis Via the Hippo Pathway

Sharif

Wellstein

2015

Future Oncol.

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Metastatic spread of cancer cells from the primary tumor site to distant organs is the major cause of death in cancer patients. To disseminate, cancer cells detach from the primary tumor, enter the blood stream and extravasate at distant organ sites such as the liver, lung, bone or brain. While cancer cells are known to evade contact inhibition during growth in culture, we found that cell density is still sensed and can signal through the Hippo pathway effectors LATS1 and YAP. These effectors control cancer cell invasive behavior into stromal tissues, expression of cytokines that recruit inflammatory cells and progression toward metastatic spread. In this perspective, we discuss the drivers and the significance of pathways controlled by cell growth density.

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“…YAP1 plays a critical role in the self-renewal of airway stem cells. Germline mutations of YAP1 predisposes for lung adenocarcinoma with high familial penetrance (68). YAP1 promotes tissue growth by regulating transcription factors including the TEADs and SMADs, and may be accompanied by chemoresistance (34).…”

Section: Discussionmentioning

confidence: 99%

Small cell lung cancer tumors and preclinical models display heterogeneity of neuroendocrine phenotypes

Zhang

Girard²,

Zhang

et al. 2018

Transl. Lung Cancer Res.

212

250

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Background: Small cell lung cancer (SCLC) is a deadly, high grade neuroendocrine (NE) tumor without recognized morphologic heterogeneity. However, over 30 years ago we described a SCLC subtype with "variant" morphology which did not express some NE markers and exhibited more aggressive growth. Methods:To quantitate NE properties of SCLCs, we developed a 50-gene expression-based NE score that could be applied to human SCLC tumors and cell lines, and genetically engineered mouse (GEM) models. We identified high and low NE subtypes of SCLC in all of our sample types, and characterized their properties. Results:We found that 16% of human SCLC tumors and 10% of SCLC cell lines were of the low NE

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R331W Missense Mutation of Oncogene YAP1 Is a Germline Risk Allele for Lung Adenocarcinoma With Medical Actionability

Abstract: These results implicated YAP1 R331W as an allele predisposed for lung adenocarcinoma with high familial penetrance. Low-dose computed tomography scans may be recommended to this subpopulation, which is at high risk for lung cancer, for personalized prevention and health management.

Cited by 86 publications

References 40 publications

Mechanisms of Hippo pathway regulation

Mechanisms of Hippo pathway regulation

Cell Density Regulates Cancer Metastasis Via the Hippo Pathway

Small cell lung cancer tumors and preclinical models display heterogeneity of neuroendocrine phenotypes

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