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https://www.readbyqxmd.com/read/28092921/the-ligand-sas-and-its-receptor-ptp10d-drive-tumour-suppressive-cell-competition
#1
Masatoshi Yamamoto, Shizue Ohsawa, Kei Kunimasa, Tatsushi Igaki
Normal epithelial cells often exert anti-tumour effects against nearby oncogenic cells. In the Drosophila imaginal epithelium, clones of oncogenic cells with loss-of-function mutations in the apico-basal polarity genes scribble or discs large are actively eliminated by cell competition when surrounded by wild-type cells. Although c-Jun N-terminal kinase (JNK) signalling plays a crucial role in this cell elimination, the initial event, which occurs at the interface between normal cells and polarity-deficient cells, has not previously been identified...
January 16, 2017: Nature
https://www.readbyqxmd.com/read/28089430/high-variability-of-expression-profiles-of-homeologous-genes-for-wnt-hh-notch-and-hippo-signaling-pathways-in-xenopus-laevis
#2
Tatsuo Michiue, Takayoshi Yamamoto, Yuuri Yasuoka, Toshiyasu Goto, Takafumi Ikeda, Kei Nagura, Takuya Nakayama, Masanori Taira, Tsutomu Kinoshita
Cell signaling pathways, such as Wnt, Hedgehog (Hh), Notch, and Hippo, are essential for embryogenesis, organogenesis, and tissue homeostasis. In this study, we analyzed 415 genes involved in these pathways in the allotetraploid frog, Xenopus laevis. Most genes are retained in two subgenomes called L and S (193 homeologous gene pairs and 29 singletons). This conservation rate of homeologs is much higher than that of all genes in the X. laevis genome (86.9% vs 60.2%). Among singletons, 24 genes are retained in the L subgenome, a rate similar to the average for all genes (82...
January 12, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28088685/a-semi-interpenetrating-network-of-polyacrylamide-and-recombinant-basement-membrane-allows-pluripotent-cell-culture-in-a-soft-ligand-rich-microenvironment
#3
Andrew J Price, Eva Y Huang, Vittorio Sebastiano, Alexander R Dunn
The physical properties of the extracellular matrix play an essential role in guiding stem cell differentiation and tissue morphogenesis both in vivo and in vitro. Existing work to investigate the role of matrix mechanics in directing stem cell proliferation, self-renewal, and differentiation has been limited by the poor attachment and survival of human pluripotent cells cultured on soft matrices (Young's modulus E ≲ 1000 Pa). To address this limitation we developed a protocol for generating semi-interpenetrating networks of polyacrylamide and recombinant basement membrane...
December 9, 2016: Biomaterials
https://www.readbyqxmd.com/read/28087714/dlg5-connects-cell-polarity-and-hippo-signaling-protein-networks-by-linking-par-1-with-mst1-2
#4
Julian Kwan, Anna Sczaniecka, Emad Heidary Arash, Liem Nguyen, Chia-Chun Chen, Srdjana Ratkovic, Olga Klezovitch, Liliana Attisano, Helen McNeill, Andrew Emili, Valeri Vasioukhin
Disruption of apical-basal polarity is implicated in developmental disorders and cancer; however, the mechanisms connecting cell polarity proteins with intracellular signaling pathways are largely unknown. We determined previously that membrane-associated guanylate kinase (MAGUK) protein discs large homolog 5 (DLG5) functions in cell polarity and regulates cellular proliferation and differentiation via undefined mechanisms. We report here that DLG5 functions as an evolutionarily conserved scaffold and negative regulator of Hippo signaling, which controls organ size through the modulation of cell proliferation and differentiation...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28079891/crb3-regulates-contact-inhibition-by-activating-the-hippo-pathway-in-mammary-epithelial-cells
#5
Xiaona Mao, Pingping Li, Yaochun Wang, Zheyong Liang, Jie Liu, Juan Li, Yina Jiang, Gang Bao, Lei Li, Bofeng Zhu, Yu Ren, Xinhan Zhao, Jianmin Zhang, Yu Liu, Jin Yang, Peijun Liu
The loss of contact inhibition is a hallmark of cancer cells. The Hippo pathway has recently been shown to be an important regulator of contact inhibition, and the cell apical polarity determinant protein CRB3 has been suggested to be involved in Hippo signalling. However, whether CRB3 regulates contact inhibition in mammary cells remains unclear, and the underlying mechanisms have not been elucidated. As shown in the present study, CRB3 decreases cell proliferation, promotes apoptosis, and enhances the formation of tight and adherens junctions...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28078823/hippo-vs-crab-tissue-specific-functions-of-the-mammalian-hippo-pathway
#6
REVIEW
Miki Nishio, Tomohiko Maehama, Hiroki Goto, Keisuke Nakatani, Wakako Kato, Hirofumi Omori, Yosuke Miyachi, Hideru Togashi, Yohei Shimono, Akira Suzuki
The Hippo signaling pathway is a vital suppressor of tumorigenesis that is often inactivated in human cancers. In normal cells, the Hippo pathway is triggered by external forces such as cell crowding, or changes to the extracellular matrix or cell polarity. Once activated, Hippo signaling down-regulates transcription supported by the paralogous cofactors YAP1 and TAZ. The Hippo pathway's functions in normal and cancer biology have been dissected by studies of mutant mice with null or conditional tissue-specific mutations of Hippo signaling elements...
January 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28076850/transforming-growth-factor-beta1-suppresses-hepatocellular-carcinoma-proliferation-via-activation-of-hippo-signaling
#7
Xiaodong Zhang, Qing Fan, Yan Li, Zhaoguo Yang, Liang Yang, Zhihong Zong, Biao Wang, Xin Meng, Qin Li, Jingang Liu, Hangyu Li
In this study, we examined the expression of core proteins of the Hippo signaling pathway in hepatocellular carcinoma (HCC) cells treated with transforming growth factor-β 1(TGF-β1) and investigated the relationship between TGF-β1 and the Hippo signaling pathway, in order to better understand their roles in HCC and their potential implications for cancer therapy. We prove that the Hippo signaling pathway is involved in the TGF-β1-induced inhibition of the growth of HCC cells. Large tumor suppressor expression (LATS1) was overexpression and yes association protein 1(YAP1) translocated from the nucleus to the cytoplasm in HCC cells treated with TGF-β1...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28076326/cytosolic-thumpd1-promotes-breast-cancer-cells-invasion-and-metastasis-via-the-akt-gsk3-snail-pathway
#8
Xiupeng Zhang, Guiyang Jiang, Mingfang Sun, Haijing Zhou, Yuan Miao, Mengyuan Liang, Enhua Wang, Yong Zhang
Human THUMP domain-containing protein 1 (THUMPD1) is a specific adaptor protein that modulates tRNA acetylation through interaction with NAT10. Immunohistochemical analysis of 146 breast cancer specimens (82 triple-negative and 64 non-triple-negative cases) indicated THUMPD1 expression is higher in breast cancer tissues (60.9%, 89/146) than normal breast tissues (28.3%, 15/53; p < 0.001). Overall and cytosolic, but not nuclear, THUMPD1 expression in breast cancer correlated with advanced TNM stage (p = 0...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28068668/the-hippo-kinases-lats1-and-2-control-human-breast-cell-fate-via-crosstalk-with-er%C3%AE
#9
Adrian Britschgi, Stephan Duss, Sungeun Kim, Joana Pinto Couto, Heike Brinkhaus, Shany Koren, Duvini De Silva, Kirsten D Mertz, Daniela Kaup, Zsuzsanna Varga, Hans Voshol, Alexandra Vissieres, Cedric Leroy, Tim Roloff, Michael B Stadler, Christina H Scheel, Loren J Miraglia, Anthony P Orth, Ghislain M C Bonamy, Venkateshwar A Reddy, Mohamed Bentires-Alj
Cell fate perturbations underlie many human diseases, including breast cancer. Unfortunately, the mechanisms by which breast cell fate are regulated are largely unknown. The mammary gland epithelium consists of differentiated luminal epithelial and basal myoepithelial cells, as well as undifferentiated stem cells and more restricted progenitors. Breast cancer originates from this epithelium, but the molecular mechanisms that underlie breast epithelial hierarchy remain ill-defined. Here, we use a high-content confocal image-based short hairpin RNA screen to identify tumour suppressors that regulate breast cell fate in primary human breast epithelial cells...
January 9, 2017: Nature
https://www.readbyqxmd.com/read/28067668/adaptor-proteins-numb-and-numbl-promote-cell-cycle-withdrawal-by-targeting-erbb2-for-degradation
#10
Maretoshi Hirai, Yoh Arita, C Jane McGlade, Kuo-Fen Lee, Ju Chen, Sylvia M Evans
Failure of trabecular myocytes to undergo appropriate cell cycle withdrawal leads to ventricular noncompaction and heart failure. Signaling of growth factor receptor ERBB2 is critical for myocyte proliferation and trabeculation. However, the mechanisms underlying appropriate downregulation of trabecular ERBB2 signaling are little understood. Here, we have found that the endocytic adaptor proteins NUMB and NUMBL were required for downregulation of ERBB2 signaling in maturing trabeculae. Loss of NUMB and NUMBL resulted in a partial block of late endosome formation, resulting in sustained ERBB2 signaling and STAT5 activation...
January 9, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28061504/dub3-deubiquitylating-enzymes-regulate-hippo-pathway-activity-by-regulating-the-stability-of-itch-lats-and-amot-proteins
#11
Hung Thanh Nguyen, Jan-Michael Kugler, Stephen M Cohen
The YAP and TAZ transcriptional coactivators promote oncogenic transformation. Elevated YAP/TAZ activity has been documented in human tumors. YAP and TAZ are negatively regulated by the Hippo tumor suppressor pathway. The activity and stability of several Hippo pathway components, including YAP/TAZ, is regulated by ubiquitin mediated protein turnover and several ubiquitin ligase complexes have been implicated in human cancer. However, little is known about the deubiquitylating enzymes that counteract these ubiquitin ligases in regulation of the Hippo pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28059560/dose-specification-for-hippocampal-sparing-whole-brain-radiotherapy-hs-wbrt-considerations-from-the-uk-hippo-trial-qa-programme
#12
Daniel Megias, Mark Phillips, Laura Clifton-Hadley, Elizabeth Harron, David J Eaton, Paul Sanghera, Gillian Whitfield
OBJECTIVES: The HIPPO trial is a UK randomised phase II trial of Hippocampal Sparing (HS) versus Conventional Whole Brain Radiotherapy after surgical resection or radiosurgery in favourable prognosis patients with 1-4 brain metastases. Each participating centre completed a planning benchmark case as part of the dedicated radiotherapy trials quality assurance programme (RTQA), promoting the safe and effective delivery of HS Intensity Modulated Radiotherapy (IMRT) in a multi-centre trial setting...
January 6, 2017: British Journal of Radiology
https://www.readbyqxmd.com/read/28055015/the-taz-mir-224-smad4-axis-promotes-tumorigenesis-in-osteosarcoma
#13
Jianjun Ma, Kangmao Huang, Yan Ma, Menglu Zhou, Shunwu Fan
Transcriptional co-activator with PDZ-binding motif (TAZ) is a downstream effector of the Hippo signaling pathway that participates in tumorigenesis. The aim of this study was to identify the miRNA counterpart for TAZ and elucidate the mechanism underlying the tumorigenic effect of TAZ. We demonstrated that TAZ is upregulated in osteosarcoma (OS) tissues and cell lines, and that TAZ overexpression can induce cell migration, invasion and proliferation. Moreover, miRNA-224 (miR-224), a TAZ phenocopy that functions downstream of TAZ, was found to be upregulated with TAZ overexpression...
January 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28052036/angiomotin-regulates-prostate-cancer-cell-proliferation-by-signaling-through-the-hippo-yap-pathway
#14
Hao Zeng, Angelica Ortiz, Peng-Fei Shen, Chien-Jui Cheng, Yu-Chen Lee, Guoyu Yu, Song-Chang Lin, Chad J Creighton, Li-Yuan Yu-Lee, Sue-Hwa Lin
Angiomotin (AMOT) is a family of proteins found to be a component of the apical junctional complex of vertebrate epithelial cells and is recently found to play important roles in neurofibromatosis type 2 (NF-2). Whether AMOT plays a role in prostate cancer (PCa) is unknown. AMOT is expressed as two isoforms, AMOTp80 and AMOTp130, which has a 409 aa N-terminal domain that is absent in AMOTp80. Both AMOTp80 and AMOTp130 are expressed in LNCaP and C4-2B4, but at a low to undetectable level in PC3, DU145, and BPH1 cells...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28051067/vgll4-targets-a-tcf4-tead4-complex-to-coregulate-wnt-and-hippo-signalling-in-colorectal-cancer
#15
Shi Jiao, Chuanchuan Li, Qian Hao, Haofei Miao, Lei Zhang, Lin Li, Zhaocai Zhou
Concerted co-regulation of multiple signalling pathways is crucial for tissue homoeostasis and tumorigenesis. Here we report that VGLL4, a previously identified YAP antagonist, also functions as a regulator of Wnt/β-catenin signalling. The expression of VGLL4 is significantly downregulated in clinical colorectal carcinoma (CRC) specimens, positively associated with patient survival rate, and inversely correlated with the expression of Wnt target genes in CRCs. Knockdown of VGLL4 enhances proliferation and tumour formation of CRC cells...
January 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28042766/insights-into-the-regulation-of-yap-taz-from-cellular-systems-and-mouse-models
#16
Wei Du, Wen Du, Mian Wan, Xuedong Zhou, Xin Xu, Liwei Zheng
The Hippo signaling pathway serves as a main regulator of tissue growth and organ size through the moderation of cell cycle dynamics across many different species. In mammals, the two downstream transcriptional regulators of this pathway are Yes-associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ). Recent studies found in addition to the core Hippo signaling pathway, other signaling pathways can also regulate YAP/TAZ activity, either directly or through crosstalk with the Hippo pathway...
January 2, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28041841/actl6a-is-co-amplified-with-p63-in-squamous-cell-carcinoma-to-drive-yap-activation-regenerative-proliferation-and-poor-prognosis
#17
Srinivas Vinod Saladi, Kenneth Ross, Mihriban Karaayvaz, Purushothama R Tata, Hongmei Mou, Jayaraj Rajagopal, Sridhar Ramaswamy, Leif W Ellisen
Loss-of-function mutations in SWI/SNF chromatin-remodeling subunit genes are observed in many cancers, but an oncogenic role for SWI/SNF is not well established. Here, we reveal that ACTL6A, encoding an SWI/SNF subunit linked to stem cell and progenitor cell function, is frequently co-amplified and highly expressed together with the p53 family member p63 in head and neck squamous cell carcinoma (HNSCC). ACTL6A and p63 physically interact, cooperatively controlling a transcriptional program that promotes proliferation and suppresses differentiation, in part through activation of the Hippo-YAP pathway via regulators including WWC1...
January 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28035666/roles-and-regulations-of-hippo-signaling-during-preimplantation-mouse-development
#18
REVIEW
Hiroshi Sasaki
During preimplantation development, mouse embryos form two types of cells, the trophoectoderm (TE) and inner cell mass (ICM), by the early blastocyst stage. This process does not require maternal factors localized in the zygotes, and embryos self-organize at the blastocyst stage through intercellular communications. In terms of the mechanisms of cell fate specification, three historical models have been proposed: the positional model, and the original and newer versions of the polarity model. Recent studies have revealed that the intercellular Hippo signaling pathway plays a central role in the specification of the first cell fates...
December 30, 2016: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/28035075/the-hippo-signaling-pathway-provides-novel-anti-cancer-drug-targets
#19
REVIEW
June Sung Bae, Sun Mi Kim, Ho Lee
The Hippo signaling pathway plays a crucial role in cell proliferation, apoptosis, differentiation, and development. Major effectors of the Hippo signaling pathway include the transcriptional co-activators Yes-associated protein 1 (YAP) and WW domain-containing transcription regulator protein 1 (TAZ). The transcriptional activities of YAP and TAZ are affected by interactions with proteins from many diverse signaling pathways as well as responses to the external environment. High YAP and TAZ activity has been observed in many cancer types, and functional dysregulation of Hippo signaling enhances the oncogenic properties of YAP and TAZ and promotes cancer development...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28031421/the-palmitoyltransferase-approximated-promotes-growth-via-the-hippo-pathway-by-palmitoylation-of-fat
#20
Hitoshi Matakatsu, Seth S Blair, Richard G Fehon
The large protocadherin Fat functions to promote Hippo pathway activity in restricting tissue growth. Loss of Fat leads to accumulation of the atypical myosin Dachs at the apical junctional region, which in turn promotes growth by inhibiting Warts. We previously identified Approximated (App), a DHHC domain palmitoyltransferase, as a negative regulator of Fat signaling in growth control. We show here that App promotes growth by palmitoylating the intracellular domain of Fat, and that palmitoylation negatively regulates Fat function...
January 2, 2017: Journal of Cell Biology
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