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https://www.readbyqxmd.com/read/29049318/short-chain-fatty-acid-receptors-inhibit-invasive-phenotypes-in-breast-cancer-cells
#1
Madhumathi Thirunavukkarasan, Chao Wang, Angad Rao, Tatsuma Hind, Yuan Ru Teo, Abrar Al-Mahmood Siddiquee, Mohamed Ally Ibrahim Goghari, Alan Prem Kumar, Deron R Herr
Short chain fatty acids (2 to 6 carbons in length) are ubiquitous lipids that are present in human plasma at micromolar concentrations. In addition to serving as metabolic precursors for lipid and carbohydrate synthesis, they also act as cognate ligands for two known G protein-coupled receptors (GPCRs), FFAR2 and FFAR3. While there is evidence that these receptors may inhibit the progression of colorectal cancer, their roles in breast cancer cells are largely unknown. We evaluated the effects of enforced overexpression of these receptors in two phenotypically distinct breast cancer cell lines: MCF7 and MDA-MD-231...
2017: PloS One
https://www.readbyqxmd.com/read/29039607/downregulation-of-mir-874-3p-promotes-chemotherapeutic-resistance-in-colorectal-cancer-via-inactivation-of-the-hippo-signaling-pathway
#2
Kaiqian Que, Yuanhe Tong, Ganbo Que, Li Li, Hongcheng Lin, Shuai Huang, Ruoyu Wang, Langlang Tang
Overcoming resistance to chemotherapy is an arduous challenge in the treatment of colorectal cancer (CRC), particularly since the underlying molecular mechanisms remain obscure. In the present study, we reported that miR‑874-3p was markedly downregulated in CRC tissues compared with that in adjacent normal colorectal epithelial tissues. Upregulation of miR-874-3p attenuated the chemoresistance of CRC cells to 5-fluorouracil (5-FU) in vitro and in vivo. Conversely, inhibition of miR-874-3p yielded an opposite effect...
October 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29017577/elevated-expression-of-par3-promotes-prostate-cancer-metastasis-by-forming-a-par3-apkc-kibra-complex-and-inactivating-the-hippo-pathway
#3
Pei-Jie Zhou, Wei Xue, Jinliang Peng, Yanqing Wang, Lianzi Wei, Ziqiang Yang, Helen He Zhu, Yu-Xiang Fang, Wei-Qiang Gao
BACKGROUND: Prostate cancer (PCa) is one of the most frequent tumors and leading cause of cancer deaths among males worldwide. The majority of deaths are due to recurrence and subsequent development of the metastatic cancer. Although loss or dislocalization of polarity proteins has been implicated in embryogenesis deficiency and tumorigenesis, association of polarity protein expression levels with tumor metastasis remains unclear. METHODS: Bioinformatics, qRT-PCR, western blot and immunohistochemical (IHC) analyses were used to examine expression of Par3, a key component of polarity-associated partitioning defective (PAR) complex, in primary and metastatic clinical PCa samples...
October 10, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29017029/fgf10-hippo-epithelial-mesenchymal-crosstalk-maintains-and-recruits-lung-basal-stem-cells
#4
Thomas Volckaert, Tingting Yuan, Cho-Ming Chao, Harold Bell, Alina Sitaula, Luisa Szimmtenings, Elie El Agha, Diptiman Chanda, Susan Majka, Saverio Bellusci, Victor J Thannickal, Reinhard Fässler, Stijn P De Langhe
The lung harbors its basal stem/progenitor cells (BSCs) in the protected environment of the cartilaginous airways. After major lung injuries, BSCs are activated and recruited to sites of injury. Here, we show that during homeostasis, BSCs in cartilaginous airways maintain their stem cell state by downregulating the Hippo pathway (resulting in increased nuclear Yap), which generates a localized Fgf10-expressing stromal niche; in contrast, differentiated epithelial cells in non-cartilaginous airways maintain quiescence by activating the Hippo pathway and inhibiting Fgf10 expression in airway smooth muscle cells (ASMCs)...
October 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28984872/p53-shades-of-hippo
#5
Noa Furth, Yael Aylon, Moshe Oren
The three p53 family members, p53, p63 and p73, are structurally similar and share many biochemical activities. Yet, along with their common fundamental role in protecting genomic fidelity, each has acquired distinct functions related to diverse cell autonomous and non-autonomous processes. Similar to the p53 family, the Hippo signaling pathway impacts a multitude of cellular processes, spanning from cell cycle and metabolism to development and tumor suppression. The core Hippo module consists of the tumor-suppressive MST-LATS kinases and oncogenic transcriptional co-effectors YAP and TAZ...
October 6, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28982981/the-hippo-pathway-regulator-kibra-promotes-podocyte-injury-by-inhibiting-yap-signaling-and-disrupting-actin-cytoskeletal-dynamics
#6
Kristin Meliambro, Jenny S Wong, Justina Ray, Rhodora C Calizo, Sara Towne, Beatriz Cole, Fadi El Salem, Ronald E Gordon, Lewis Kaufman, John C He, Evren U Azeloglu, Kirk N Campbell
Kidney podocytes represent a key constituent of the glomerular filtration barrier. Identifying the molecular mechanisms of podocyte injury and survival is important for better understanding and management of kidney diseases. KIBRA (KIdney BRAin protein), an upstream regulator of the Hippo signaling pathway encoded by the Wwc1 gene, shares the pro-injury properties of its putative binding partner dendrin and antagonizes the pro-survival signaling of the downstream Hippo pathway effector YAP (Yes-associated protein) in Drosophila and MCF10A cells...
October 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28973878/yap-taz-cdc42-signaling-regulates-vascular-tip-cell-migration
#7
Masahide Sakabe, Jieqing Fan, Yoshinobu Odaka, Ning Liu, Aishlin Hassan, Xin Duan, Paige Stump, Luke Byerly, Megan Donaldson, Jiukuan Hao, Marcus Fruttiger, Qing Richard Lu, Yi Zheng, Richard A Lang, Mei Xin
Angiogenesis and vascular remodeling are essential for the establishment of vascular networks during organogenesis. Here we show that the Hippo signaling pathway effectors YAP and TAZ are required, in a gene dosage-dependent manner, for the proliferation and migration of vascular endothelial cells (ECs) during retinal angiogenesis. Intriguingly, nuclear translocation of YAP and TAZ induced by Lats1/2-deletion blocked endothelial migration and phenocopied Yap/Taz-deficient mutants. Furthermore, overexpression of a cytoplasmic form of YAP (YAPS127D) partially rescued the migration defects caused by loss of YAP and TAZ function...
September 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28972170/%C3%AE-1-integrin-dependent-rac-group-i-pak-signaling-mediates-yap-activation-of-yes-associated-protein-1-yap1-via-nf2-merlin
#8
Hiba Sabra, Molly Brunner, Vinay Mandati, Bernhard Wehrle Haller, Dominique Lallemand, Anne-Sophie Ribba, Genevieve Chevalier, Philippe Guardiola, Marc R Block, Daniel Bouvard
Cell adhesion to the extracellular matrix or to surrounding cells plays a key role in cell proliferation and differentiation, and is critical for proper tissue homeostasis. An important pathway in adhesion-dependent cell proliferation is the Hippo signaling cascade, which is coregulated by the transcription factors Yes-associated protein 1 (YAP1) and transcriptional coactivator with PDZ-binding motif (TAZ). However, how cells integrate extracellular information at the molecular level to regulate YAP1 nuclear localization is still puzzling...
September 29, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28969054/usp21-regulates-hippo-pathway-activity-by-mediating-mark-protein-turnover
#9
Hung Thanh Nguyen, Jan-Michael Kugler, Anand C Loya, Stephen M Cohen
The Hippo pathway, which acts to repress the activity of YAP and TAZ trancriptional co-activators, serve as a barrier for oncogenic transformation. Unlike other oncoproteins, YAP and TAZ are rarely activated by mutations or amplified in cancer. However, elevated YAP/TAZ activity is frequently observed in cancer and often correlates with worse survival. The activity and stability of Hippo pathway components, including YAP/TAZ, AMOT and LATS1/2, are regulated by ubiquitin-mediated protein degradation. Aberrant expression of ubiquitin ligase complexes that regulate the turnover of Hippo components and deubiquitylating enzymes that counteract these ubiquitin ligases have been implicated in human cancer...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28969031/down-regulation-of-lincrna-p21-contributes-to-gastric-cancer-development-through-hippo-independent-activation-of-yap
#10
Ying Chen, Guoqing Wei, Hongwei Xia, Huangfei Yu, Qiuling Tang, Feng Bi
Long intergenic non-coding RNA p21 (lincRNA-p21), known as the direct transcriptional target of p53, was found down-regulated in several human solid tumors. However, little is known about the role of lincRNA-p21 in gastric cancer. The expression levels of lincRNA-p21 in tissue samples and cell lines were detected by qRT-PCR. MGC-803 and MKN-45 cells were transfected with siRNAs targeting lincRNA-p21 or control siRNAs to determine the effect of reduced lincRNA-p21 expression on tumorigenesis. We also overexpressed lincRNA-p21 in MGC-803 cells...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28964625/regulation-of-the-hippo-pathway-transcription-factor-tead
#11
REVIEW
Kimberly C Lin, Hyun Woo Park, Kun-Liang Guan
The TEAD transcription factor family is best known for transcriptional output of the Hippo signaling pathway and has been implicated in processes such as development, cell growth and proliferation, tissue homeostasis, and regeneration. Our understanding of the functional importance of TEADs has increased dramatically since its initial discovery three decades ago. The majority of our knowledge of TEADs is in the context of Hippo signaling as nuclear DNA-binding proteins passively activated by Yes-associated protein (YAP) and transcriptional activator with PDZ-binding domain (TAZ), transcription coactivators downstream of the Hippo pathway...
September 27, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28963395/lncrna-wires-up-hippo-and-hedgehog-signaling-to-reprogramme-glucose-metabolism
#12
Xin Zheng, Han Han, Guang-Ping Liu, Yan-Xiu Ma, Ruo-Lang Pan, Ling-Jie Sang, Rui-Hua Li, Luo-Jia Yang, Jeffrey R Marks, Wenqi Wang, Aifu Lin
The Hippo pathway plays essential roles in organ size control and cancer prevention via restricting its downstream effector, Yes-associated protein (YAP). Previous studies have revealed an oncogenic function of YAP in reprogramming glucose metabolism, while the underlying mechanism remains to be fully clarified. Accumulating evidence suggests long noncoding RNAs (lncRNAs) as attractive therapeutic targets, given their roles in modulating various cancer-related signaling pathways. In this study, we report that lncRNA breast cancer anti-estrogen resistance 4 (BCAR4) is required for YAP-dependent glycolysis...
September 28, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28962630/%C3%AE-catenin-mediated-yap-signaling-promotes-human-glioma-growth
#13
Yan Wang, Peng Pan, Zhaohao Wang, Yu Zhang, Peng Xie, Decheng Geng, Yang Jiang, Rutong Yu, Xiuping Zhou
BACKGROUND: Hippo/YAP pathway is known to be important for development, growth and organogenesis, and dysregulation of this pathway leads to tumor progression.We and others find that YAP is up-regulated in human gliomas and associated with worse prognosis of patients. However, the role and mechanism of YAP in glioma progression is largely unknown. METHODS: The expression of YAP in glioma tissues was detected by quantitative polymerase chain reaction (qPCR) and immunoblotting...
September 29, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28960584/effect-of-the-acylation-of-tead4-on-its-interaction-with-co-activators-yap-and-taz
#14
Yannick Mesrouze, Marco Meyerhofer, Fedir Bokhovchuk, Patrizia Fontana, Catherine Zimmermann, Typhaine Martin, Clara Delaunay, Aude Izaac, Joerg Kallen, Tobias Schmelzle, Dirk Erdmann, Patrick Chène
The Hippo pathway is deregulated in various cancers, and the discovery of molecules that modulate this pathway may open new therapeutic avenues in oncology. TEAD transcription factors are the most distal elements of the Hippo pathway and their transcriptional activity is regulated by the YAP protein. Amongst the various possibilities for targeting this pathway, inhibition of the YAP:TEAD interaction is an attractive strategy. It has been shown recently that TEAD proteins are covalently linked via a conserved cysteine to a fatty acid molecule (palmitate) that binds to a deep hydrophobic cavity present in these proteins...
September 28, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28957532/arrhythmogenic-cardiomyopathy-pathology-genetics-and-concepts-in-pathogenesis
#15
Edgar T Hoorntje, Wouter P Te Rijdt, Cynthia A James, Kalliopi Pilichou, Cristina Basso, Daniel P Judge, Connie R Bezzina, J Peter van Tintelen
Arrhythmogenic cardiomyopathy (ACM) is a rare, heritable heart disease characterized by fibro-fatty replacement of the myocardium and a high degree of electric instability. It was first thought to be a congenital disorder, but is now regarded as a dystrophic heart muscle disease that develops over time. There is no curative treatment and current treatment strategies focus on attenuating the symptoms, slowing disease progression, and preventing life-threatening arrhythmias and sudden cardiac death. Identification of mutations in genes encoding desmosomal proteins and in other genes has led to insights into the disease pathogenesis and greatly facilitated identification of family members at risk...
October 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28947533/rho-differentially-regulates-the-hippo-pathway-by-modulating-the-interaction-between-amot-and-nf2-in-the-blastocyst
#16
Xianle Shi, Zixi Yin, Bin Ling, Lingling Wang, Chang Liu, Xianhui Ruan, Weiyu Zhang, Lingyi Chen
The Hippo pathway modulates the transcriptional activity of Yap to regulate the differentiation of the inner cell mass (ICM) and the trophectoderm (TE) in blastocysts. Yet, how Hippo signaling is differentially regulated in ICM and TE cells is poorly understood. Through an inhibitor/activator screen, we identified Rho as a negative regulator of Hippo in TE cells, and PKA as a positive regulator of Hippo in ICM cells. We further elucidated a novel mechanism for Rho to suppress Hippo, distinct to the prevailing view that Rho inhibits Hippo signaling through modulating cytoskeleton remodeling and/or cell polarity...
September 25, 2017: Development
https://www.readbyqxmd.com/read/28943241/yap-taz-and-hedgehog-coordinate-growth-and-patterning-in-gastrointestinal-mesenchyme
#17
Jennifer L Cotton, Qi Li, Lifang Ma, Joo-Seop Park, Jiayi Wang, Jianhong Ou, Lihua J Zhu, Y Tony Ip, Randy L Johnson, Junhao Mao
YAP/TAZ are the major mediators of mammalian Hippo signaling; however, their precise function in the gastrointestinal tract remains poorly understood. Here we dissect the distinct roles of YAP/TAZ in endodermal epithelium and mesenchyme and find that, although dispensable for gastrointestinal epithelial development and homeostasis, YAP/TAZ function as the critical molecular switch to coordinate growth and patterning in gut mesenchyme. Our genetic analyses reveal that Lats1/2 kinases suppress expansion of the primitive mesenchymal progenitors, where YAP activation also prevents induction of the smooth muscle lineage through transcriptional repression of Myocardin...
October 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28942149/fibulin-5-promotes-airway-smooth-muscle-cell-proliferation-and-migration-via-modulating-hippo-yap-taz-pathway
#18
Jia Fu, Mao Zheng, Xiaofang Zhang, Yufeng Zhang, Yao Chen, Hua Li, Xiaowei Wang, Jinjun Zhang
Asthma is a common chronic disease mainly occurs from childhood. Increased airway smooth muscle mass is involved in the pathogenesis of asthma. Fibulin-5 was upregulated in the lung tissues of patients with COPD and idiopathic pulmonary fibrosis. This study aimed to investigate Fibulin-5 expression in asthmatic patients and the effect and mechanism of Fibulin-5 on the proliferation and migration of airway smooth muscle cells (ASMCs). The expression of Fibulin-5, YAP, and TAZ in the induced sputum of 38 asthmatic children (19 mild and 19 moderate asthmatics) and 19 healthy controls was determined...
November 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28938438/targeted-disruption-of-yap-and-taz-impairs-the-maintenance-of-the-adrenal-cortex
#19
Adrien Levasseur, Guillaume St-Jean, Marilène Paquet, Derek Boerboom, Alexandre Boyer
Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are functionally redundant transcriptional regulators that are downstream effectors of the Hippo signaling pathway. They act as major regulators of stem cell maintenance, cell growth and differentiation. To characterize their roles in the adrenal cortex, we generated a mouse model in which Yap and Taz were conditionally deleted in steroidogenic cells (Yapflox/flox;Tazflox/flox;Nr5a1cre/+). Male Yapflox/flox;Tazflox/flox;Nr5a1cre/+ mice were characterized by an age-dependent degeneration of the adrenal cortex associated with an increase in apoptosis and a progressive reduction in the expression levels of steroidogenic genes...
September 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/28935017/-role-of-hippo-signaling-pathway-in-lung-cancer
#20
Yuechao Liu, Ying Xing, Li Cai
Lung cancer is the leading cause of cancer related mortality in the world, with more than 1 million deaths per year, accounting for about one fifth of all cancer deaths worldwide. Over the past years, lung cancer treatment has been based on surgery, radiation therapy, chemotherapy, targeted therapies, and immunotherapy, but the improvement is not very perfect. Therefore, it has become clear that additional therapeutic strategies are urgently required to provide an improved survival benefit for patients. In recent years, Hippo signaling pathway has become a popular direction in the field of cancer research...
September 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
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