Xueying Zhang, Xinxin Liu, Fadi Li, Xiangpeng Yue
Colostrum and milk proteins are essential resources for the growth and development of the newborns, while their kinds and amounts vary greatly during the lactation period. This study was conducted to better understand whey proteome and its changes at six lactation time points (0 d, 3 d, 7 d, 14 d, 28 d, and 56 d after lambing) in Hu sheep. Using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF/TOF MS) technologies, a total of 52 differentially expressed protein spots (DEPS), corresponding to 25 differentially expressed proteins (DEPs), were obtained...
October 1, 2020: Animals: An Open Access Journal From MDPI
Natalie M Landry, Ian M C Dixon
Cardiac fibroblast activation to hyper-synthetic myofibroblasts following a pathological stimulus or in response to a substrate with increased stiffness may be a key tipping point for the evolution of cardiac fibrosis. Cardiac fibrosis per se is associated with progressive loss of heart pump function and is a primary contributor to heart failure. While TGF-β is a common cytokine stimulus associated with fibroblast activation, a druggable target to quell this driver of fibrosis has remained an elusive therapeutic goal due to its ubiquitous use by different cell types and also in the signaling complexity associated with SMADs and other effector pathways...
October 2, 2020: Cellular Signalling
Alexandre Pj Martin, Jacques H Camonis
The proper segregation of basic elements such as the compartmentalization of the genome and the shuttling of macromolecules between the nucleus and the cytoplasm is a crucial mechanism for homeostasis maintenance in eukaryotic cells. XPO1 (Exportin 1) is the major nuclear export receptor and is required for the export of proteins and RNAs out of the nucleus. STK38 (also known as NDR1) is a Hippo pathway serine/threonine kinase with multifarious functions in normal and cancer cells. In this review, we summarize the history of the discovery of the nucleo/cytoplasmic shuttling of proteins and focus on the major actor of nuclear export: XPO1...
October 5, 2020: Cell Cycle
Jianan Zheng, Hui Yu, Anqi Zhou, Bingfeng Wu, Jiayi Liu, Yinan Jia, Lin Xiang
Hippo pathway is a chain of kinases consists of a series of protein kinases and transcription factors. Meanwhile, oxidative stress is a condition of elevated concentrations of reactive oxygen species (ROS) that cause molecular damage to vital structures and functions. Both of them are key regulators in cell proliferation, survival, and development. These processes are strictly regulated by highly coordinated mechanisms, including c-Jun n-terminal kinase (JNK) pathway, mTOR pathway and a number of extrinsic and intrinsic factors...
October 4, 2020: Cell Cycle
Priyakshi Kalita-de Croft, Malcolm Lim, Haarika Chittoory, Xavier M de Luca, Jamie R Kutasovic, Bryan W Day, Fares Al-Ejeh, Peter T Simpson, Amy E McCart Reed, Sunil R Lakhani, Jodi M Saunus
Background: Human epidermal growth factor receptor-4 (HER4) and yes-associated protein-1 (YAP) are candidate therapeutic targets in oncology. YAP's transcriptional coactivation function is modulated by the HER4 intracellular domain (HER4-ICD) in vitro , but the clinical relevance of this has not been established. This study investigated the potential for targeting the HER4-YAP pathway in brain metastatic breast cancer. Methods: We performed immuno-phenotypic profiling of pathway markers in a consecutive breast cancer series with 25 years of clinical follow up ( n  = 371), and patient-matched breast and metastatic brain tumours ( n  = 91; 30 pairs)...
2020: Therapeutic Advances in Medical Oncology
Hengyang Shen, Yixuan Meng, Tao Hu, Shuwei Li, Mulong Du, Junyi Xin, Dongying Gu, Meilin Wang, Zan Fu
The Hippo signalling pathway plays a crucial role in carcinogenesis. Therefore, we hypothesized that genetic variants in genes related to this pathway are associated with the colorectal cancer risk. A case-control study including 1150 patients and 1342 controls was performed to assess the association of genetic variants of genes involved in the Hippo signalling pathway with the risk of colorectal cancer. The results were corrected for multiple comparisons using the false discovery rate (FDR). We used a regression model to determine the effects of single-nucleotide polymorphisms (SNPs) on the survival of patients with colorectal cancer in The Cancer Genome Atlas (TCGA) datasets...
October 3, 2020: Archives of Toxicology
Qiuyun Tian, Xiaofang Fan, Jianshe Ma, Yujiao Han, Dantong Li, Shan Jiang, Fukun Zhang, Hui Guang, Xiaoqiong Shan, Ran Chen, Ping Wang, Qing Wang, Jinge Yang, Yongyu Wang, Lianggang Hu, Yangping Shentu, Yongsheng Gong, Junming Fan
Resveratrol, a type of natural polyphenol mainly extracted from the skin of grapes, has been reported to protect against inflammatory responses and exert anxiolytic effect. Yes-associated protein (YAP), a major downstream effector of the Hippo signaling pathway, plays a critical role in inflammation. The present study aimed to explore whether YAP pathway was involved in the anxiolytic effect of resveratrol in lipopolysaccharide (LPS)-treated C57BL/6 J male mice. LPS treatment induced anxiety-like behavior and decreased sirtuin 1 while increased YAP expression in the hippocampus...
September 30, 2020: Toxicology and Applied Pharmacology
Joonwoo Park, Ga Hee Kim, Jeonggeun Lee, Bui Thi Chau Phuong, Byounguk Kong, Ji Eun Won, Gun Woo Won, Yong Hee Lee, Hee Dong Han, YoungJoo Lee
Mammalian sterile 20-like kinase 1/2 (MST1/2) plays an important role in cell growth and apoptosis and functions as a tumor suppressor. Previously, we showed that MST2 overexpression activates Estrogen receptor alpha (ERα) in human breast cancer MCF-7 cells in the absence of a ligand. Here, we examined the role of MST2 in the growth of ER-positive MCF-7 cells. Cell cycle, apoptosis, and mammosphere formation assay method were implemented to detect the biological effects of MST2 ablation on the growth of MCF-7 cells in vitro...
September 29, 2020: Toxicology and Applied Pharmacology
Veronica Veschi, Giorgio Stassi
The role of Hippo pathway in colorectal cancer (CRC) initiation and progression has been controversial. In this issue of Cell Stem Cell, Cheung et al. (2020) shed new light on a distinct function of the transcriptional co-activator YAP as a tumor suppressor and Wnt pathway inhibitor in CRC.
October 1, 2020: Cell Stem Cell
Sharanya Sivanand, Matthew G Vander Heiden
Cancer cells must adapt metabolism to thrive despite nutrient limitations in the tumor microenvironment. In this issue of Genes & Development , King and colleagues (pp. 1345-1358) report a role for transcriptional regulators of the Hippo pathway to facilitate protein scavenging and support proliferation under some nutrient-deprived conditions.
October 1, 2020: Genes & Development
Liya Jiang, Juan Li, Chenxing Zhang, Yufeng Shang, Jun Lin
Yes‑associated protein (YAP) acts as a transcriptional co‑activator in gene expression and cell proliferation control by binding to the transcriptional factor TEA domain (TEAD) of the Hippo signaling pathway in the nucleus, and also acts as a regulator by binding to another transcriptional co‑activator, β‑catenin of the Wnt signaling pathway. Whether YAP preferentially acts as a transcriptional co‑regulator of the activity of the Hippo signaling pathway or as a regulator in the Wnt signaling pathway depends on the cell type...
November 2020: Molecular Medicine Reports
Annie Wai Yeeng Chai, Pei San Yee, Stacey Price, Shi Mun Yee, Hui Mei Lee, Vivian Kh Tiong, Emanuel Gonçalves, Fiona M Behan, Jessica Bateson, James Gilbert, Aik Choon Tan, Ultan McDermott, Mathew J Garnett, Sok Ching Cheong
New therapeutic targets for oral squamous cell carcinoma (OSCC) are urgently needed. We conducted genome-wide CRISPR-Cas9 screens in 21 OSCC cell lines, primarily derived from Asians, to identify genetic vulnerabilities that can be explored as therapeutic targets. We identify known and novel fitness genes and demonstrate that many previously identified OSCC-related cancer genes are non-essential and could have limited therapeutic value, while other fitness genes warrant further investigation for their potential as therapeutic targets...
September 29, 2020: ELife
Carmen Terren, Carine Munaut
Cryopreservation and transplantation of ovarian tissue represent a promising fertility preservation technique for prepubertal patients or for patients requiring urgent oncological management. However, this technique has some limitations, including follicular loss directly after transplantation mainly due to ischaemic damage but also due to activation of primordial follicles (also known as follicular burnout), leading to follicular reserve loss in the graft and thereby potentially reducing its lifespan. In vitro and in vivo studies indicate that the phosphatidylinositol-3-kinase (PI3K)/phosphatase and tensin homologue (PTEN)/Akt, mammalian target of rapamycin (mTOR), c-Jun-N-terminal kinase (JNK), and Hippo signalling pathways are involved in primordial follicle activation...
September 28, 2020: Reproductive Sciences
Kana Hasegawa, Shinsuke Fujii, Shinji Matsumoto, Yudai Tajiri, Akira Kikuchi, Tamotsu Kiyoshima
Most cancer cells are exposed to altered extracellular environments, such as an increase in extracellular matrix (ECM) stiffness and soluble signals consisting of growth factors and cytokines. It is therefore conceivable that changes in tumor extracellular environments affect tumor cell behavior. The Hippo pathway reportedly responds to the extracellular environment and regulates the nuclear localization of the transcription co-activator, yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ)...
September 28, 2020: Journal of Pathology
Asunción Espinosa-Sánchez, Elisa Suárez-Martínez, Laura Sánchez-Díaz, Amancio Carnero
The theory of cancer stem cells (CSCs) proposes that the different cells within a tumor, as well as metastasis deriving from it, are originated from a single subpopulation of cells with self-renewal and differentiation capacities. These cancer stem cells are supposed to be critical for tumor expansion and metastasis, tumor relapse and resistance to conventional therapies, such as chemo- and radiotherapy. The acquisition of these abilities has been attributed to the activation of alternative pathways, for instance, WNT, NOTCH, SHH, PI3K, Hippo, or NF-κB pathways, that regulate detoxification mechanisms; increase the metabolic rate; induce resistance to apoptotic, autophagic, and senescence pathways; promote the overexpression of drug transporter proteins; and activate specific stem cell transcription factors...
2020: Frontiers in Oncology
Toshihide Nishimura, Ákos Végvári, Haruhiko Nakamura, Harubumi Kato, Hisashi Saji
Epidermal growth factor receptor EGFR major driver mutations may affect downstream molecular networks and pathways, which would influence treatment outcomes of non-small cell lung cancer (NSCLC). This study aimed to unveil profiles of mutant proteins expressed in lung adenocarcinomas of 36 patients harboring representative driver EGFR mutations (Ex19del, nine; L858R, nine; no Ex19del/L858R, 18). Surprisingly, the orthogonal partial least squares discriminant analysis performed for identified mutant proteins demonstrated the profound differences in distance among the different EGFR mutation groups, suggesting that cancer cells harboring L858R or Ex19del emerge from cellular origins different from L858R/Ex19del-negative cells...
2020: Frontiers in Oncology
Yixian Guo, Xu Liu, Danhua Xu, Chen Huang, Zeyu Wang, Xiang Xia, Chunchao Zhu, Jia Xu, Zizhen Zhang, Yanying Shen, Wenyi Zhao, Gang Zhao
Background: Gastric cancer (GC) remains a refractory cancer particularly in Eastern Asia. Large tumor suppressor kinases 1/2 (LATS1/2) are core members of the Hippo pathway. The role of LATS1/2 in the prognosis of different subtypes of advanced gastric cancer and its relationship with the tumor immune microenvironment in GC remain unknown. Exploring the role of LATS1/2 in GC might provide potential immunotherapeutic approaches for treating GC. Methods: Four hundred and ninety surgically resected primary GC samples were assessed for LATS1/2, CD8, FOXP3, and CD163...
2020: Frontiers in Oncology
Majid Gholipour, Arezoo Tabrizi
Introduction: The role of Hippo signaling pathway, which was identified by genetic studies as a key regulator for tissue growth and organ size, in promoting physiological cardiac hypertrophy has not been investigated. Methods: Fourteen male Wistar rats were randomly assigned to the exercise and control groups. The exercise group ran 1 hour per day, 5 days/week, at about 65%-75% VO2max on the motor-driven treadmill with 15º slope, and the control group ran 15 min/d, 2 days/week at 9 m/min (0º inclination), throughout the eight-week experimental period...
2020: BioImpacts: BI
Yuchen Liu, Xiaohui Wang, Yingzi Yang
Primary liver cancer is one of the most common cancer worldwide. Hepatocellular carcinoma (HCC) in particular, is the second leading cause of cancer deaths in the world. The Hippo signaling pathway has emerged as a major oncosuppressive pathway that plays critical roles inhibiting hepatocyte proliferation, survival, and HCC formation. A key component of the Hippo pathway is the inhibition of yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) transcription factors by the Hippo kinase cascade...
September 28, 2020: Clinical and Molecular Hepatology
Ai-Wen Shen, Li-Li Fu, Lu Lin, Bo Sun, Dong-Xu Song, Wu-Tao Wang, Yi-Hao Wang, Pei-Ran Yin, Sheng-Qiang Yu
Autosomal dominant polycystic kidney disease (ADPKD) is a complex process, involving the alteration of multiple genes and signaling pathways, and the pathogenesis of ADPKD remains largely unknown. Here, we demonstrated the suppressive role of sorting nexin 9 (SNX9) during ADPKD development. Sorting nexin 9 expression was detected in the kidney tissues of ADPKD patients, for the first time, and SNX9 expression was also detected in Pkd1 knockout ( Pkd1 -/- ) and control mice. Subsequently, a series of gain- and loss-of-function studies were performed, to explore the biological roles and underlying molecular mechanisms of SNX9 in ADPKD progression...
2020: Frontiers in Cell and Developmental Biology
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