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Hippo signalling

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https://www.readbyqxmd.com/read/29452146/the-hippo-yap1-pathway-interacts-with-fgfr1-signaling-to-maintain-stemness-in-lung-cancer
#1
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
https://www.readbyqxmd.com/read/29449645/egfr-pi3k-pdk1-pathway-regulates-yap-signaling-in-hepatocellular-carcinoma-the-mechanism-and-its-implications-in-targeted-therapy
#2
Hongwei Xia, Xinyu Dai, Huangfei Yu, Sheng Zhou, Zhenghai Fan, Guoqing Wei, Qiulin Tang, Qiyong Gong, Feng Bi
The epidermal growth factor receptor (EGFR) pathway and Hippo signaling play an important role in the carcinogenesis of hepatocellular carcinoma (HCC). However, the crosstalk between these two pathways and its implications in targeted therapy remains unclear. We found that the activated EGFR signaling could bypass RhoA to promote the expression of YAP(Yes-associated protein), the core effector of the Hippo signaling, and its downstream target Cyr61. Further studies indicated that EGFR signaling mainly acted through the PI3K-PDK1 (Phosphoinositide 3-kinase-Phosphoinositide-dependent kinase-1) pathway to activate YAP, but not the AKT and MAPK pathways...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29445137/metabolic-features-of-cancer-stem-cells-the-emerging-role-of-lipid-metabolism
#3
REVIEW
Rita Mancini, Alessia Noto, Maria Elena Pisanu, Claudia De Vitis, Marcello Maugeri-Saccà, Gennaro Ciliberto
Cancer stem cells (CSCs) are an uncommon subset of tumor cells capable of self-renewal, differentiating, and recreating the parental tumor when transplanted into the murine background. Over the past two decades, efforts toward understanding CSC biology culminated into identifying a set of signaling pathways sustaining "stemness". Nevertheless, while metabolic rewiring is nowadays considered a hallmark of cancer, no consensus has been reached on the metabolic features underlying the plastic nature of CSCs, which are capable of residing in a dormant state, and able to rapidly proliferate when the need to repopulate the tumor mass arises...
February 15, 2018: Oncogene
https://www.readbyqxmd.com/read/29443735/identification-of-gene-expression-models-for-laryngeal-squamous-cell-carcinoma-using-co-expression-network-analysis
#4
Chun-Wei Yang, Shu-Fang Wang, Xiang-Li Yang, Lin Wang, Lin Niu, Ji-Xiang Liu
One of the most common head and neck cancers is laryngeal squamous cell carcinoma (LSCC). LSCC exhibits high mortality rates and has a poor prognosis. The molecular mechanisms leading to the development and progression of LSCC are not entirely clear despite genetic and therapeutic advances and increased survival rates. In this study, a total of 116 differentially expressed genes (DEGs), including 11 upregulated genes and 105 downregulated genes, were screened from LSCC samples and compared with adjacent noncancerous...
February 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29440430/posh-regulates-hippo-signaling-through-ubiquitin-mediated-expanded-degradation
#5
Xianjue Ma, Xiaowei Guo, Helena E Richardson, Tian Xu, Lei Xue
The Hippo signaling pathway is a master regulator of organ growth, tissue homeostasis, and tumorigenesis. The activity of the Hippo pathway is controlled by various upstream components, including Expanded (Ex), but the precise molecular mechanism of how Ex is regulated remains poorly understood. Here we identify Plenty of SH3s (POSH), an E3 ubiquitin ligase, as a key component of Hippo signaling in Drosophila POSH overexpression synergizes with loss of Kibra to induce overgrowth and up-regulation of Hippo pathway target genes...
February 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29440237/tension-dependent-regulation-of-mammalian-hippo-signaling-through-limd1
#6
Consuelo Ibar, Elmira Kirichenko, Benjamin Keepers, Edward Enners, Katelyn Fleisch, Kenneth D Irvine
Hippo signaling is regulated by biochemical and biomechanical cues that influence the cytoskeleton, but the mechanisms that mediate this have remained unclear. We show that all three mammalian Ajuba family proteins - AJUBA, LIMD1, and WTIP - exhibit tension-dependent localization to adherens junctions, and that both Lats family proteins, LATS1 and LATS2, exhibit an overlapping tension-dependent junctional localization. This localization of Ajuba and Lats family proteins is also influenced by cell density, and by Rho activation...
February 13, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29440144/spon2-promotes-m1-like-macrophage-recruitment-and-inhibits-hepatocellular-carcinoma-metastasis-by-distinct-integrin-rho-gtpase-hippo-pathways
#7
Yan-Li Zhang, Qing Li, Xiao-Mei Yang, Fang Fang, Jun Li, Ya-Hui Wang, Qin Yang, Lei Zhu, Hui-Zhen Nie, Xue-Li Zhang, Ming-Xuan Feng, Shu-Heng Jiang, Guang-Ang Tian, Li-Peng Hu, Ho-Young Lee, Su-Jae Lee, Qiang Xia, Zhi-Gang Zhang
Tumor-associated macrophages (TAM) represent key regulators of the complex interplay between cancer and the immune microenvironment. Matricellular protein SPON2 is essential for recruiting lymphocytes and initiating immune responses. Recent studies have shown that SPON2 has complicated roles in cell migration and tumor progression. Here we report that, in the tumor microenvironment of hepatocellular carcinoma (HCC), SPON2 not only promotes infiltration of M1-like macrophages but also inhibits tumor metastasis...
February 13, 2018: Cancer Research
https://www.readbyqxmd.com/read/29439714/tfap2c-promotes-stemness-and-chemotherapeutic-resistance-in-colorectal-cancer-via-inactivating-hippo-signaling-pathway
#8
Xu Wang, Di Sun, Jiandong Tai, Si Chen, Miao Yu, Dong Ren, Lei Wang
BACKGROUND: Aberrant expression of transcription Factor AP-2 Gamma (TFAP2C) has been reported to be implicated in malignant process of many cancers. The purpose of this study is to investigate the clinical significance and biological roles of TFAP2C in colorectal cancer (CRC). METHODS: TFAP2C expression was evaluated by real-time PCR, Western blot and immunohistochemistry (IHC) respectively in clinical CRC tissues. Statistical analysis was performed to explore the correlation between TFAP2C expression and clinicopathological features, and overall and progression-free survival in CRC patients...
February 13, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29438698/programming-of-schwann-cells-by-lats1-2-taz-yap-signaling-drives-malignant-peripheral-nerve-sheath-tumorigenesis
#9
Lai Man Natalie Wu, Yaqi Deng, Jincheng Wang, Chuntao Zhao, Jiajia Wang, Rohit Rao, Lingli Xu, Wenhao Zhou, Kwangmin Choi, Tilat A Rizvi, Marc Remke, Joshua B Rubin, Randy L Johnson, Thomas J Carroll, Anat O Stemmer-Rachamimov, Jianqiang Wu, Yi Zheng, Mei Xin, Nancy Ratner, Q Richard Lu
Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive Schwann cell (SC)-lineage-derived sarcomas. Molecular events driving SC-to-MPNST transformation are incompletely understood. Here, we show that human MPNSTs exhibit elevated HIPPO-TAZ/YAP expression, and that TAZ/YAP hyperactivity in SCs caused by Lats1/2 loss potently induces high-grade nerve-associated tumors with full penetrance. Lats1/2 deficiency reprograms SCs to a cancerous, progenitor-like phenotype and promotes hyperproliferation...
February 12, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29438691/hippo-stampede-in-nerve-sheath-tumors
#10
M Laura Feltri, Yannick Poitelon
Current therapies for malignant peripheral nerve sheath tumors (MPNSTs) are ineffective. The study by Wu et al. in this issue of Cancer Cell provides evidence that the HIPPO pathway is overactive in human MPNSTs and that combined modulation of LATS1/2-YAP/TAZ and PDGFR signaling in Schwann cells reduces MPNST growth.
February 12, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29437787/reg%C3%AE-controls-hippo-signaling-and-reciprocal-nf-%C3%AE%C2%BAb-yap-regulation-to-promote-colon-cancer
#11
Xiaotao Li, Qingwei Wang, Xiao Gao, Tong Yu, Lei Yuan, Jie Dai, Weicang Wang, Geng Chen, Chan Jiao, Wang Zhou, Quan Huang, Long Cui, Pei Zhang, Robb E Moses, Jianhua Yang, Fengyuan Chen, Junjiang Fu, Jianru Xiao, Lei Li, Yongyan Dang
PURPOSE: Colorectal cancer (CRC) is one of the most commonly diagnosed cancers closely associated with inflammation and hyperactive growth. We have previously demonstrated a regulatory circuit between the proteasome activator REGγ and NF-kappaB (NF-κB) during colon inflammation, known to be important in the development of colitis-associated cancer as well as sporadic CRC. How the inflammatory microenvironment affects the Hippo pathway during CRC development is largely unknown. EXPERIMENTAL DESIGN: Here, we used REGγ deficient colon cancer cell lines, REGγ knockout mice and human CRC samples to identify the novel molecular mechanism by which REGγ functions as an oncoprotein in the development of colorectal cancer...
February 6, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29436693/yap-regulates-gastric-cancer-survival-and-migration-via-sirt1-mfn2-mitophagy
#12
Hongzhu Yan, Chengmin Qiu, Weiwei Sun, Minmin Gu, Feng Xiao, Jue Zou, Li Zhang
Gastric cancer is the fifth most common cancer worldwide and Hippo-Yap is the novel signaling pathway which plays an important role in gastric cancer tumor development and progression. However, little insight is available to date regarding the specific role of Yes-associated protein (Yap) in gastric cancer. In the present study, we identified the mechanism through which Yap sustains gastric cancer viability and migration. Yap was greatly upregulated in gastric cancer cells and its expression promoted cellular migration and survival...
February 7, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29435056/furin-inhibitor-d6r-suppresses-epithelial-mesenchymal-transition-in-sw1990-and-patu8988-cells-via-the-hippo-yap-signaling-pathway
#13
Meng Zhou, Youli Zhang, Hong Wei, Junbo He, Dawei Wang, Baoding Chen, Jian Zeng, Aihua Gong, Min Xu
Hexa-D-arginine (D6R), an inhibitor of furin, has potential therapeutic applications in different types of human tumor. However, the function of D6R in targeting pancreatic cancer cells remains to be elucidated. In the present study, the proliferation, invasion and migration abilities of SW1990 and PaTu8988 cells were examined using a Cell Counting Kit-8, and Transwell and wound healing assays. Subsequently, the expression of proteins associated with epithelial-mesenchymal transition (EMT) and the Hippo-yes-associated protein (YAP) pathway were detected using western blot analysis...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29435044/soft-shelled-turtle-peptide-modulates-microrna-profile-in-human-gastric-cancer-ags-cells
#14
Yi-Chen Wu, Xiang Liu, Jiu-Li Wang, Xiang-Liu Chen, Lan Lei, Jing Han, You-Shui Jiang, Zhi-Qiang Ling
Cancer prevention using natural micronutrition on epigenetic mechanisms primarily revolves around plant extracts. However, the role of macronutrition, including animal peptides, on epigenetic modification in cancer has been elusive. In traditional Chinese medicine, the soft-shelled turtle has a long-history of being a functional food that strengthens immunity through unknown mechanisms. The present study aimed to investigate the impact of soft-shelled turtle peptide on microRNA (miRNA) expression in gastric cancer (GC) cells and to analyze the potential anticancer mechanisms for GC...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29432919/yap1-is-essential-for-osteoclastogenesis-through-a-teads-dependent-mechanism
#15
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 9, 2018: Bone
https://www.readbyqxmd.com/read/29431744/a-histone-deacetylase-3-dependent-pathway-delimits-peripheral-myelin-growth-and-functional-regeneration
#16
Xuelian He, Liguo Zhang, Luis F Queme, Xuezhao Liu, Andrew Lu, Ronald R Waclaw, Xinran Dong, Wenhao Zhou, Grahame Kidd, Sung-Ok Yoon, Andres Buonanno, Joshua B Rubin, Mei Xin, Klaus-Armin Nave, Bruce D Trapp, Michael P Jankowski, Q Richard Lu
Deficits in Schwann cell-mediated remyelination impair functional restoration after nerve damage, contributing to peripheral neuropathies. The mechanisms mediating block of remyelination remain elusive. Here, through small-molecule screening focusing on epigenetic modulators, we identified histone deacetylase 3 (HDAC3; a histone-modifying enzyme) as a potent inhibitor of peripheral myelinogenesis. Inhibition of HDAC3 enhanced myelin growth and regeneration and improved functional recovery after peripheral nerve injury in mice...
February 12, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29415512/linking-extracellular-matrix-agrin-to-the-hippo-pathway-in-liver-cancer-and-beyond
#17
REVIEW
Sayan Chakraborty, Wanjin Hong
In addition to the structural and scaffolding role, the extracellular matrix (ECM) is emerging as a hub for biomechanical signal transduction that is frequently relayed to intracellular sensors to regulate diverse cellular processes. At a macroscopic scale, matrix rigidity confers long-ranging effects contributing towards tissue fibrosis and cancer. The transcriptional co-activators YAP/TAZ, better known as the converging effectors of the Hippo pathway, are widely recognized for their new role as nuclear mechanosensors during organ homeostasis and cancer...
February 6, 2018: Cancers
https://www.readbyqxmd.com/read/29410983/nanotopography-regulates-motor-neuron-differentiation-of-human-pluripotent-stem-cells
#18
Weiqiang Chen, Shuo Han, Weiyi Qian, Shinuo Weng, Haiou Yang, Yubing Sun, Luis G Villa-Diaz, Paul H Krebsbach, Jianping Fu
The regulation of human pluripotent stem cell (hPSC) behaviors has been mainly studied through exploration of biochemical factors. However, the current directed differentiation protocols for hPSCs that completely rely on biochemical factors remain suboptimal. It has recently become evident that coexisting biophysical signals in the stem cell microenvironment, including nanotopographic cues, can provide potent regulatory signals to mediate adult stem cell behaviors, including self-renewal and differentiation...
February 7, 2018: Nanoscale
https://www.readbyqxmd.com/read/29408652/the-hippo-pathway-as-a-drug-target-in-gastric-cancer
#19
Yiting Qiao, Tongyu Li, Shusen Zheng, Hangxiang Wang
The Hippo tumor suppressor pathway is critical for balancing cellular differentiation and proliferation in response to cell-cell contact, mechanical signals and diffusible signals such as lysophosphatidic acid. Hippo pathway signaling is frequently dysregulated in gastric cancer (GC), as well as many other kinds of solid tumors, contributing to multiple aspects of malignant progression including unchecked cell division and metastasis. Considering the importance of this Hippo pathway in cancer, its pharmacological disruption may be of huge benefit in the fight against this disease...
January 30, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29400692/hippo-mediated-suppression-of-irs2-akt-signaling-prevents-hepatic-steatosis-and-liver-cancer
#20
Sun-Hye Jeong, Han-Byul Kim, Min-Chul Kim, Ji-Min Lee, Jae Ho Lee, Jeong-Hwan Kim, Jin-Woo Kim, Woong-Yang Park, Seon-Young Kim, Jae Bum Kim, Haeryoung Kim, Jin-Man Kim, Hueng-Sik Choi, Dae-Sik Lim
Nonalcoholic fatty liver disease (NAFLD) is a major risk factor for liver cancer; therefore, its prevention is an important clinical goal. Ablation of phosphatase and tensin homolog (PTEN) or the protein kinase Hippo signaling pathway induces liver cancer via activation of AKT or the transcriptional regulators YAP/TAZ, respectively; however, the potential for crosstalk between the PTEN/AKT and Hippo/YAP/TAZ pathways in liver tumorigenesis has thus far remained unclear. Here, we have shown that deletion of both PTEN and SAV1 in the liver accelerates the development of NAFLD and liver cancer in mice...
February 5, 2018: Journal of Clinical Investigation
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