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Sang Yeon Cho, Jang Wook Gwak, Yoo Chul Shin, Daeju Moon, Jihyuok Ahn, Hyon Woo Sol, Sungha Kim, Gwanghun Kim, Hyun Mu Shin, Kyung Ha Lee, Ji Yeon Kim, Jin Soo Kim
Yes-associated protein 1 (YAP1) is a transcriptional regulator of the Hippo pathway, which regulates the development and progression of a number of types of cancer, including that of the colon. In the present study, the expression levels of Hippo pathway genes and their clinical significance were investigated in 458 patients with colon adenocarcinoma (COAD), the most frequently diagnosed neoplastic disease globally, using data obtained from The Cancer Genome Atlas database. Notably, mRNA expression of YAP1 was higher in COAD than in other types of gastrointestinal tract cancer...
April 2018: Oncology Letters
Carole Sourbier, Pei-Jyun Liao, Christopher J Ricketts, Darmood Wei, Youfeng Yang, Sarah M Baranes, Benjamin K Gibbs, Lernik Ohanjanian, L Spencer Krane, Bradley T Scroggins, J Keith Killian, Ming-Hui Wei, Toshiki Kijima, Paul S Meltzer, Deborah E Citrin, Len Neckers, Cathy D Vocke, W Marston Linehan
Papillary renal cell carcinomas (PRCC) are a histologically and genetically heterogeneous group of tumors that represent 15-20% of all kidney neoplasms and may require diverse therapeutic approaches. Alteration of the NF2 tumor suppressor gene, encoding a key regulator of the Hippo signaling pathway, is observed in 22.5% of PRCC. The Hippo signaling pathway controls cell proliferation by regulating the transcriptional activity of Yes-Associated Protein, YAP1. Loss of NF2 results in aberrant YAP1 activation...
February 13, 2018: Oncotarget
Jiaolong Shi, Fengping Li, Xingxing Yao, Tingyu Mou, Zhijun Xu, Zheng Han, Siyu Chen, Wende Li, Jiang Yu, Xiaolong Qi, Hao Liu, Guoxin Li
Trastuzumab is the only target to be approved as the first-line treatment of HER2 positive metastatic gastric cancer, but ubiquitous resistance decreases its therapeutic benefit. In this study, we found HER4, phosphorylation HER4 (p-HER4) and the mesenchymal marker Vimentin increased in trastuzumab-resistant cells (MKN45TR and NCI-N87TR), while epithelial markers expressions in trastuzumab-resistant cell lines and animal models decreased. Additionally, silencing HER4 prevented the epithelial-mesenchymal transition and led to decreased proliferation and migration in vitro and in vivo...
March 14, 2018: Oncogene
Hiroki Goto, Miki Nishio, Yoko To, Tatsuya Oishi, Yosuke Miyachi, Tomohiko Maehama, Hiroshi Nishina, Haruhiko Akiyama, Tak Wah Mak, Yuma Makii, Taku Saito, Akihiro Yasoda, Noriyuki Tsumaki, Akira Suzuki
Hippo signaling is modulated in response to cell density, external mechanical forces, or rigidity of the extracellular matrix (ECM). The Mps one binder kinase activator (MOB) adaptor proteins are core components of Hippo signaling and have important effects on Yes-associated protein-1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ), which are potent transcriptional regulators. YAP1/TAZ are key contributors to cartilage and bone development but the molecular mechanisms by which the Hippo pathway controls chondrogenesis are largely unknown...
March 6, 2018: Development
De-Wei Wu, Yao-Chen Wang, Lee Wang, Chih Yi Chen, Huei Lee
Purpose: MicroRNA-630 plays dual roles in apoptosis and drug resistance in human cancers. However, the role of miR-630 in resistance to tyrosine kinase inhibitors (TKIs) in lung adenocarcinoma remains to be elucidated. Methods: Manipulation of miR-630 and its targeted gene YAP1 and/or combination of inhibitor treatments was performed to explore whether low miR-630 could confer TKI resistance due to de-targeting YAP1, and this could decrease proapoptotic protein Bad expression through the miR-630/YAP1/ERK feedback loop...
2018: Theranostics
Ling Guo, Ting Cai, Keng Chen, Rong Wang, Jiaxin Wang, Chunhong Cui, Jifan Yuan, Kuo Zhang, Zhongzhen Liu, Yi Deng, Guozhi Xiao, Chuanyue Wu
Precise control of mesenchymal stem cell (MSC) differentiation is critical for tissue development and regeneration. We show here that kindlin-2 is a key determinant of MSC fate decision. Depletion of kindlin-2 in MSCs is sufficient to induce adipogenesis and inhibit osteogenesis in vitro and in vivo. Mechanistically, kindlin-2 regulates MSC differentiation through controlling YAP1/TAZ at both the transcript and protein levels. Kindlin-2 physically associates with myosin light-chain kinase in response to mechanical cues of cell microenvironment and intracellular signaling events and promotes myosin light-chain phosphorylation...
March 1, 2018: Journal of Cell Biology
Shuai Ye, Matthew A Lawlor, Adrian Rivera-Reyes, Shaun Egolf, Susan Chor, Koreana Pak, Gabrielle E Ciotti, Avery C Lee, Gloria Marino, Jennifer Shah, David Niedzwicki, Kristy Weber, Paul M C Park, Md Zahidul Alam, Alison Grazioli, Malay Haldar, Mousheng Xu, Jennifer A Perry, Jun Qi, T S Karin Eisinger-Mathason
To date, no consistent oncogenic driver mutations have been identified in most adult soft tissue sarcomas; these tumors are thus generally insensitive to existing targeted therapies. Here we investigated alternate mechanisms underlying sarcomagenesis to identify potential therapeutic interventions. Undifferentiated pleomorphic sarcoma (UPS) is an aggressive tumor frequently found in skeletal muscle where deregulation of the Hippo pathway and aberrant stabilization of its transcriptional effector yes-associated protein 1 (YAP1) increases proliferation and tumorigenesis...
February 28, 2018: Cancer Research
Di Li, Jia-Xuan Ji, Yi-Tian Xu, Hai-Bo Ni, Qin Rui, Hui-Xiang Liu, Feng Jiang, Rong Gao, Gang Chen
AIMS: To investigate the roles of Lats1/p-YAP1 pathway in TBI-induced neuronal apoptosis and neurological deficits in rats. RESULTS: We found that Lats1 and YAP1 were expressed in cerebral cortex neurons of Sprague-Dawley rats, and the phosphorylation levels of Lats1 and YAP1 in injured regions were significantly increased after TBI. Furthermore, inhibition of Lats1 not only decreased the level of p-YAP1, but also attenuated neuronal apoptosis and neurological impairment...
February 27, 2018: CNS Neuroscience & Therapeutics
Soon Auck Hong, Si-Hyong Jang, Mee-Hye Oh, Sung Joon Kim, Jin-Hyung Kang, Sook-Hee Hong
EGFR tyrosine kinase inhibitor (EGFR TKI) is approved as first-line treatment for advanced-stage EGFR mutant lung adenocarcinoma (LADC). Yes-associated protein 1 (YAP1), a main effector of the Hippo pathway, is associated with adverse prognosis and disruption of EGFR TKI modulation of non-small cell lung cancer. In this study, we demonstrated a prognostic role of YAP1 in EGFR mutant LADC and efficacy of EGFR TKI therapy. A total of 63 patients, including 41 with paired lung cancer specimens before and after EGFR TKI therapy and 22 with non-paired lung cancer specimens prior to EGFR TKI, were enrolled for examination...
February 3, 2018: Pathology, Research and Practice
Xueqian Wang, Haitao Hou, Kaida Song, Zhiqiang Zhang, Shuqiang Zhang, Ying Cao, Liming Chen, Qing Sang, Fang Lin, Hui Xu
LPA signaling plays important roles during cell migration and proliferation in normal and pathological conditions. However, its role during sensory organ development remains unknown. Here we show a LPA receptor Lpar2b is expressed in the posterior lateral line primordium (pLLP) and mechanosensory organs called neuromasts (NMs) in zebrafish embryos. Lpar2b loss-of-function significantly reduces the number of NMs and hair cells in the posterior lateral line (pLL). Further analysis reveals that Lpar2b regulates the patterning and tissue size of the pLLP...
2018: Frontiers in Molecular Neuroscience
Ahmed Elbediwy, Barry J Thompson
Mechanical stretch forces can control the growth of epithelial tissues such as mammalian skin, whose surface area is precisely coordinated with body size. In skin keratinocytes cultured in vitro, mechanical forces acting via Integrin adhesions and the actin cytoskeleton have been shown to induce nuclear translocation of YAP/TAZ co-activators to induce cell proliferation. Furthermore, conditional knockouts of both YAP (also called YAP1) and TAZ (also called WWTR1) in mouse skin resemble the phenotype of skin-specific loss of Integrin beta1 (ITGB1), indicating that this signalling mechanism is important in vivo...
February 21, 2018: Current Opinion in Cell Biology
Juan Tan, Mei Liu, Jun-Ying Zhang, Yue-Liang Yao, Yan-Xia Wang, Yong Lin, Kang Song, Jiao Tan, Jin-Rong Wu, You-Hong Cui, Yan Wang, Xiu-Wu Bian
Capillary morphogenesis protein 2 (CMG2) was originally identified through its participation in capillary morphogenesis, and subsequently identified as the second receptor for anthrax toxin (ANTXR2). Although tumor-associated functions of CMG2 have also been reported, the clinical significance and functional mechanism of CMG2 in glioma remain to be elucidated. We assessed the clinicopathological relevance of CMG2 in a cohort of 48 glioma patients as well as through public glioma databases, and explored the function of CMG2 using glioblastoma (GBM) models in vitro and in vivo...
February 23, 2018: Journal of Pathology
Tingting Lu, Ziming Li, Ying Yang, Wenxiang Ji, Yongfeng Yu, Xiaomin Niu, Qingyu Zeng, Weiliang Xia, Shun Lu
The Hippo pathway plays a critical role in organ size control, tissue homeostasis and tumor genesis through its key transcription regulator Yes-associated protein1 (YAP1), but the mechanism underlying its role in lung cancer is unclear. We hypothesized that YAP1 influences FGFR1 signaling to maintain cancer stem-like cell (CSC) properties in FGFR1-amplified lung cancer. In support of this, our data confirms that expression levels of YAP1 are positively associated with those of FGFR1 in clinical lung carcinoma samples as measured by real-time PCR, western blot, and immunohistochemistry (IHC) staining...
February 13, 2018: Cancer Letters
Lei Li, Tongzheng Liu, Yunhui Li, Chenming Wu, Kuntian Luo, Yujiao Yin, Yuping Chen, Somaira Nowsheen, Jinhuan Wu, Zhenkun Lou, Jian Yuan
The Yes-associated protein 1 (YAP1), a major downstream effector of the Hippo pathway, functions as a transcriptional regulator and has an important role in cellular control of organ size and tumor growth. Elevated oncogenic activity of YAP1 has been clarified in different types of human cancers, which contributes to cancer cell survival and chemoresistance. However, the molecular mechanism of YAP1 overexpression in cancer is still not clear. Here we demonstrate that the deubiquitination enzyme USP9X deubiquitinates and stabilizes YAP1, thereby promoting cancer cell survival...
February 16, 2018: Oncogene
Jai-Nien Tung, Po-Lin Lin, Yao-Chen Wang, De-Wei Wu, Chi-Yi Chen, Huei Lee
Programmed death ligand (PD-L1) expression was associated with tumor immune escape and subsequent poor prognosis in non-small cell lung cancer (NSCLC). This expression was higher in patients with EGFR-mutated NSCLC tumors than in those with EGFR-wild-type (WT) NSCLC tumors. We therefore hypothesized that poor prognosis mediated by higher PD-L1 may be partially through conferring resistance to tyrosine kinase inhibitor (TKI) in NSCLC regardless of EGFR mutation. The change in PD-L1 expression following gene manipulation corresponded with changes in expression of HIF-1α and YAP1...
January 12, 2018: Oncotarget
Liming Zhao, Hanfeng Guan, Chao Song, Yuting Wang, Changyu Liu, Cong Cai, Hao Zhu, Hui Liu, Libo Zhao, Jun Xiao
Yes-associated protein 1 (YAP1), the core effector of the Hippo signaling pathway, has been identified as a key regulator of tissue homeostasis and organ development by controlling cell proliferation and differentiation. Previous studies have shown that YAP1 regulates multiple steps during skeletal development and bone remodeling, including the self-renewal and differentiation of mesenchymal stem cells (MSCs). However, its role in osteoclastogenesis remains largely unknown. Here, we report that YAP1 is an essential regulator for osteoclast differentiation and activity...
February 10, 2018: Bone
Chunlin Ou, Zhenqiang Sun, Xiayu Li, Xiaoling Li, Weiguo Ren, Zailong Qin, Xuemei Zhang, Weitang Yuan, Jia Wang, Wentao Yu, Shiwen Zhang, Qiu Peng, Qun Yan, Wei Xiong, Guiyuan Li, Jian Ma
No abstract text is available yet for this article.
February 8, 2018: Cancer Letters
Jiantao Xiao, Qing Shi, Weiguo Li, Xingyu Mu, Jintao Peng, Mingzi Li, Mulin Chen, Huabing Huang, Chenji Wang, Kun Gao, Jie Fan
The α-arrestins domain-containing 1 and 3 (ARRDC1 and ARRDC3) are two members of the α-arrestins family. Yes-associated protein 1 (YAP1) is a key downstream transcription co-activator of the Hippo pathway essential for cancer initiation, progression, or metastasis in clear cell renal cell carcinoma (ccRCC). The aim of this work was to elucidate the role of the α-arrestins in ccRCC tumorigenesis by identifying molecular interacting factors and exploring potential mechanisms. In this study, we identified YAP1 as a novel ARRDC3 interacting protein in RCC cells through tandem affinity purification and mass spectrometry...
2018: American Journal of Cancer Research
Andrew Fesler, Hua Liu, Jingfang Ju
Despite advances in colon cancer treatments, resistance and recurrence remain a significant challenge in treating patients. Novel therapeutic strategies are in urgent need to overcome resistance and improve patient outcomes. MicroRNA based therapeutics have potential to help combat resistance. In this study, we have shown that low miR-15a expression correlates with poor patient prognosis. We have demonstrated the therapeutic potential of miR-15a in colon cancer. miR-15a inhibits several important genes (BCL2, BMI1, YAP1 and DCLK1), decreasing cancer progression and resistance...
January 5, 2018: Oncotarget
Kirti Gupta, Swathi Jugunoori, Ayusman Satapathy, Pravin Salunke, Narendra Kumar, Bishan Dass Radotra, Rakesh Kumar Vasishta
The World Health Organization classification of central nervous system neoplasms (2016 update) recognizes four histological variants and genetically defined molecular subgroups within medulloblastoma (MB). MB with myogenic differentiation is one of the rare variant which is usually recognized as a pattern alongside the known histological variants. Due to its rarity, less is known about its molecular landscape and importantly about its placement in the current molecular schema. We aimed to analyze this rare variant for expression of three immunohistochemical markers conventionally used in molecular stratification of MB...
February 2, 2018: Human Pathology
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