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https://www.readbyqxmd.com/read/27912098/characterization-of-hippo-pathway-components-by-gene-inactivation
#1
Steven W Plouffe, Zhipeng Meng, Kimberly C Lin, Brian Lin, Audrey W Hong, Justin V Chun, Kun-Liang Guan
The Hippo pathway is important for regulating tissue homeostasis, and its dysregulation has been implicated in human cancer. However, it is not well understood how the Hippo pathway becomes dysregulated because few mutations in core Hippo pathway components have been identified. Therefore, much work in the Hippo field has focused on identifying upstream regulators, and a complex Hippo interactome has been identified. Nevertheless, it is not always clear which components are the most physiologically relevant in regulating YAP/TAZ...
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27912060/the-hippo-pathway-kinases-lats1-2-suppress-cancer-immunity
#2
Toshiro Moroishi, Tomoko Hayashi, Wei-Wei Pan, Yu Fujita, Matthew V Holt, Jun Qin, Dennis A Carson, Kun-Liang Guan
Poorly immunogenic tumor cells evade host immunity and grow even in the presence of an intact immune system, but the complex mechanisms regulating tumor immunogenicity have not been elucidated. Here, we discovered an unexpected role of the Hippo pathway in suppressing anti-tumor immunity. We demonstrate that, in three different murine syngeneic tumor models (B16, SCC7, and 4T1), loss of the Hippo pathway kinases LATS1/2 (large tumor suppressor 1 and 2) in tumor cells inhibits tumor growth. Tumor regression by LATS1/2 deletion requires adaptive immune responses, and LATS1/2 deficiency enhances tumor vaccine efficacy...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27911857/yap1-regulates-abcg2-and-cancer-cell-side-population-in-human-lung-cancer-cells
#3
Yuyuan Dai, Shu Liu, Wen-Qian Zhang, Yi-Lin Yang, Phillip Hang, Hui Wang, Li Cheng, Ping-Chih Hsu, Yu-Chen Wang, Zhidong Xu, David M Jablons, Liang You
A small population of cancer cells called cancer-initiating cells or cancer stem cells (CSCs) are involved in drug resistance, metastasis, and cancer relapse. Finding pathways that regulate CSC is very important for clinical therapy. ATP-binding cassette sub-family G member 2 (ABCG2) plays a role in side population (SP) cell formation and contributes to chemotherapy resistance in common forms of cancer. Yes-associated protein 1 (YAP1) is a major transcriptional effector of the Hippo pathway, which plays important roles in organ size control and tumorigenesis...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27907036/the-characteristic-of-s100a7-induction-by-the-hippo-yap-pathway-in-cervical-and-glossopharyngeal-squamous-cell-carcinoma
#4
Fei Kong, Yunguang Li, Enze Hu, Rui Wang, Junhao Wang, Jin Liu, Jinsan Zhang, Dacheng He, Xueyuan Xiao
S100A7 is expressed in many squamous cell carcinomas (SCCs). Our previous study revealed that S100A7 was dramatically induced in several SCC cells and activation of the Hippo pathway significantly promoted S100A7 in epidermoid carcinoma cells. However, whether the Hippo pathway regulates S100A7 expression in SCCs remains largely unknown. Here, we uncover that S100A7 induction by the Hippo-YAP pathway displays different characteristic in cervical and glossopharyngeal SCC. In well differentiated HCC94 cervical cells and FaDu pharyngeal cells, S100A7 is easily induced by both suspension and dense culture, which is accompanied by an increase in YAP phosphorylation and a decrease in nuclear YAP...
2016: PloS One
https://www.readbyqxmd.com/read/27903710/the-hippo-p53-pathway-in-megakaryopoiesis
#5
EDITORIAL
Praveen K Suraneni, John D Crispino
No abstract text is available yet for this article.
December 2016: Haematologica
https://www.readbyqxmd.com/read/27900010/a-novel-mutation-of-the-fat2-gene-in-spinal-meningioma
#6
Genshu Tate, Koji Kishimoto, Toshiyuki Mitsuya
Meningiomas may be classified as neurofibromin 2 (NF2)-associated and non-NF2 meningiomas depending on the presence or absence of molecular alterations in the NF2 gene. One of the characteristic histological features of meningiomas is the whorl formation of neoplastic arachnoid cells. NF2 is a human homolog of the Drosophila gene, Merlin (Mer). In humans, NF2 is the gene responsible for the disease neurofibromatosis type II, which results in the development of brain tumors, including acoustic neurinoma and meningioma...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895316/investigating-cytokinesis-failure-as-a-strategy-in-cancer-therapy
#7
Callum McKenzie, Pier Paolo D'Avino
Effective therapeutics exploit common characteristics shared amongst cancers. As many cancers present chromosomal instability (CIN), one possible approach to treat these cancers could be to increase their CIN above a threshold that would affect their viability. Here, we investigated whether causing polyploidy by cytokinesis failure could represent a useful approach. We show that cytokinesis failure caused by depletion of Citron kinase (CIT-K) dramatically decreased cell proliferation in breast, cervical and colorectal cancer cells...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27885187/-role-of-hippo-yap-taz-signaling-pathway-in-mechanotransduction
#8
Erika Ishihara, Hiroshi Nishina
Transcriptional coactivators YAP(yes associated protein)and TAZ(transcriptional coactivator with PDZ-binding motif)regulate gene expression through binding to transcription factors. Recently, some studies showed that YAP/TAZ activity responded to mechanical inputs such as stiffness of the extracellular matrix and the mechanical regulation of YAP/TAZ controlled cell proliferation or differentiation. Additionally, we revealed important roles of YAP in tissue formation and homeostasis through cellular tension and pressure...
2016: Clinical Calcium
https://www.readbyqxmd.com/read/27883091/mycobacterium-tuberculosis-triggered-hippo-pathway-orchestrates-cxcl1-2-expression-to-modulate-host-immune-responses
#9
Monoranjan Boro, Vikas Singh, Kithiganahalli Narayanaswamy Balaji
Mycobacterium tuberculosis (Mtb) pathogenesis encompasses a plethora of finely regulated alterations within the host which eventually coin the outcome of infection. Chemokines are important components in directing immune cell recruitment to the site of infection, and shaping the disease progression. Here, we demonstrate that Hippo (mammalian sterile 20-like 1 and 2 kinases, MST1/2, in mammals), is activated during mycobacterial infection in a toll-like receptor (TLR) 2-interleukin receptor-1 associated kinases (IRAK1/4)-dependent manner...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27881410/taz-activation-drives-fibroblast-spheroid-growth-expression-of-pro-fibrotic-paracrine-signals-and-context-dependent-ecm-gene-expression
#10
Amy J Jorgenson, Kyoung Moo Choi, Delphine Sicard, Karry M J Smith, Samantha E Hiemer, Xaralabos Varelas, Daniel J Tschumperlin
Recent studies have implicated the Hippo pathway and its transcriptional effectors YAP and TAZ as necessary for fibroblast activation and tissue fibrosis. To test the specific and sufficient roles for TAZ in driving autonomous fibroblast activation, we cultured NIH3T3 fibroblasts expressing a doxycycline-inducible nuclear-localized mutant of TAZ (TAZ4SA) in scaffold-free 3D hanging drop spheroids, or on matrices of specified mechanical rigidity. Control NIH3T3 fibroblasts formed spheroids in hanging drop culture that remained stable and neither increased nor decreased in size significantly over 15 days...
November 23, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27881216/interacting-network-of-hippo-wnt-%C3%AE-catenin-and-notch-signaling-represses-liver-tumor-formation
#11
Wantae Kim, Sanjoy Kumar Khan, Yingzi Yang
Acquiring a selective growth advantage by breaking the proliferation barrier established by gatekeeper genes is a centrally important event in tumor formation. Removal of mammalian Hippo kinase Mst1 and Mst2 in hepatocytes leads to very rapid hepatocellular carcinoma (HCC) formation, indicating that the Hippo signaling pathway is a critical gatekeeper in hepatocytes that restrains abnormal growth. By rigorous genetic approaches, we have identified an interacting network of the Hippo, Wnt/β-catenin and Notch signaling pathways that controls organ size and HCC development...
November 24, 2016: BMB Reports
https://www.readbyqxmd.com/read/27877230/transcriptional-cofactor-mask2-is-required-for-yap-induced-cell-growth-and-migration-in-bladder-cancer-cell
#12
Liang Dong, Fan Lin, Wanjun Wu, Weiren Huang, Zhiming Cai
The highly conserved Hippo signaling pathway is an important pathway involved in tumorigenesis and development. In previous studies, YAP, the transcription coactivator of Hippo pathway, is found to be highly expressed in many clinical bladder cancer samples. To investigate the function of YAP and its cofactor Mask2 in bladder cancer, we overexpress YAP in bladder cancer cells and discover that YAP is able to promote bladder cancer cell growth and migration. In addition, we provide evidence that knockdown of Mask2 is able to repress bladder cancer cell growth and migration...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27875740/conditional-knockout-of-tfpi-1-in-vsmcs-of-mice-accelerates-atherosclerosis-by-enhancing-amot-yap-pathway
#13
Jiajun Xiao, Kaiyue Jin, Jiping Wang, Jing Ma, Jin Zhang, Nan Jiang, Huijun Wang, Xinping Luo, Jian Fei, Zhugang Wang, Xiao Yang, Duan Ma
BACKGROUND: Tissue factor pathway inhibitor-1 (TFPI-1) has multiple functions and its precise role and molecular mechanism during the development of atherosclerosis are not clear. OBJECTIVES: To determine the effect and molecular mechanism of TFPI-1 deficiency in vascular smooth muscle cells (VSMCs) in atherosclerosis in the apolipoprotein E knockout (ApoE(-/-)) mouse. METHODS AND RESULTS: A mouse model with a conditional knockout of TFPI-1 in VSMCs in an atherosclerosis-prone background (ApoE(-/-)) was generated...
November 12, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27874005/the-hippo-signalling-pathway-coordinates-organ-growth-and-limits-developmental-variability-by-controlling-dilp8-expression
#14
Emilie Boone, Julien Colombani, Ditte S Andersen, Pierre Léopold
Coordination of organ growth during development is required to generate fit individuals with fixed proportions. We recently identified Drosophila Dilp8 as a key hormone in coupling organ growth with animal maturation. In addition, dilp8 mutant flies exhibit elevated fluctuating asymmetry (FA) demonstrating a function for Dilp8 in ensuring developmental stability. The signals regulating Dilp8 activity during normal development are not yet known. Here, we show that the transcriptional co-activators of the Hippo (Hpo) pathway, Yorkie (Yki, YAP/TAZ) and its DNA-binding partner Scalloped (Sd), directly regulate dilp8 expression through a Hpo-responsive element (HRE) in the dilp8 promoter...
November 22, 2016: Nature Communications
https://www.readbyqxmd.com/read/27869648/hippo-signaling-interactions-with-wnt-%C3%AE-catenin-and-notch-signaling-repress-liver-tumorigenesis
#15
Wantae Kim, Sanjoy Kumar Khan, Jelena Gvozdenovic-Jeremic, Youngeun Kim, Jason Dahlman, Hanjun Kim, Ogyi Park, Tohru Ishitani, Eek-Hoon Jho, Bin Gao, Yingzi Yang
Malignant tumors develop through multiple steps of initiation and progression, and tumor initiation is of singular importance in tumor prevention, diagnosis, and treatment. However, the molecular mechanism whereby a signaling network of interacting pathways restrains proliferation in normal cells and prevents tumor initiation is still poorly understood. Here, we have reported that the Hippo, Wnt/β-catenin, and Notch pathways form an interacting network to maintain liver size and suppress hepatocellular carcinoma (HCC)...
November 21, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27869165/tap63-suppresses-mammary-tumorigenesis-through-regulation-of-the-hippo-pathway
#16
X Su, M Napoli, H A Abbas, A Venkatanarayan, N H B Bui, C Coarfa, Y J Gi, F Kittrell, P H Gunaratne, D Medina, J M Rosen, F Behbod, E R Flores
Mechanisms regulating the transition of mammary epithelial cells (MECs) to mammary stem cells (MaSCs) and to tumor-initiating cells (TICs) have not been entirely elucidated. The p53 family member, p63, is critical for mammary gland development and contains transactivation domain isoforms, which have tumor-suppressive activities, and the ΔN isoforms, which act as oncogenes. In the clinic, p63 is often used as a diagnostic marker, and further analysis of the function of TAp63 in the mammary gland is critical for improved diagnosis and patient care...
November 21, 2016: Oncogene
https://www.readbyqxmd.com/read/27868197/expression-of-a-hepatitis-b-virus-pre-s2-deletion-mutant-in-the-liver-results-in-hepatomegaly-and-hepatocellular-carcinoma-in-mice
#17
Yuan-Chi Teng, Jenq Chyuan Neo, Jaw-Ching Wu, Yi-Fan Chen, Cheng-Heng Kao, Ting-Fen Tsai
Hepatocellular carcinoma (HCC) is the most common form of liver cancer and has a poor prognosis and a low survival rate; its incidence is on the rise. Hepatitis B virus (HBV) infection is one of the main causes of HCC. A high prevalence of pre-S deletions of HBV surface antigen, which encompass T-cell and/or B-cell epitopes, is found in HBV carriers; antiviral therapy and viral immune escape may cause and select for these HBV mutants. In particular, the presence of pre-S2 deletion mutants is an important risk factor associated with cirrhosis and HCC...
November 21, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27864128/prostaglandin-e2-activates-yap-and-a-positive-signaling-loop-to-promote-colon-regeneration-following-colitis-but-also-carcinogenesis-in-mice
#18
Han-Byul Kim, Minchul Kim, Young-Soo Park, Intae Park, Tackhoon Kim, Sung-Yeun Yang, Charles J Cho, DaeHee Hwang, Jin-Hak Jung, Sanford D Markowitz, Sung Wook Hwang, Suk-Kyun Yang, Dae-Sik Lim, Seung-Jae Myung
BACKGROUND & AIMS: Prostaglandin E2 (PGE2) is mediator of inflammation that regulates tissue regeneration, but its continual activation has been associated with carcinogenesis. Little is known about factors in the PGE2 signaling pathway that contribute to tumor formation. We investigated whether yes associated protein 1 (YAP1), a transcriptional co-activator in the Hippo signaling pathway, mediates PGE2 function. METHODS: DLD-1 and SW480 colon cancer cell lines were transfected with vectors expressing transgenes or small hairpin RNAs and incubated with recombinant PGE2, with or without pharmacologic inhibitors of signaling proteins, and analyzed by immunoblot, immunofluorescence, quantitative reverse transcription PCR, transcriptional reporter, and proliferation assays...
November 15, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27862246/a-retrospective-analysis-of-mortality-in-captive-pygmy-hippopotamus-choeropsis-liberiensis-from-1912-to-2014
#19
Gabriella L Flacke, Suzana Tkalčić, Beatrice Steck, Kristin Warren, Graeme B Martin
The pygmy hippopotamus (Choeropsis liberiensis) is an IUCN Red List Endangered species (CITES Appendix II) that has been housed in zoological collections since 1912. As wild populations continue to decline throughout the species' range, successful ex situ breeding and management, including an understanding of morbidity and mortality, are of utmost importance. This study is the first comprehensive review of mortality data from the captive population since 1982 and significantly expands on previous analyses. We solicited necropsy reports from 129/187 zoological institutions worldwide that currently or previously held pygmy hippos and received data for 404 animals (177 ♂, 220 ♀, 7 undermined sex), representing 43% of pygmy hippos that have died in captivity...
November 2016: Zoo Biology
https://www.readbyqxmd.com/read/27856247/the-drosophila-f-box-protein-slimb-controls-dsmurf-protein-turnover-to-regulate-the-hippo-pathway
#20
Liangchang Hu, Ping Wang, Runan Zhao, Shanshan Li, Feng Wang, Chaojie Li, Lei Cao, Shian Wu
SMAD ubiquitination regulatory factors 1 and 2 (Smurf1/2) are members of the HECT domain E3 ligase family which play crucial roles in the regulation of cell cycle progression, planar cell polarity, cancer metastasis and cell apoptosis. We recently showed that the Drosophila homolog dSmurf controls the stability of Warts kinase to regulate the Hippo pathway. In the current study, we found that the F-box protein Slimb controls dSmurf protein level to regulate the Hippo pathway. Slimb physically associates with dSmurf as revealed by co-immunoprecipitation assay in S2 cells...
November 14, 2016: Biochemical and Biophysical Research Communications
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