keyword
https://read.qxmd.com/read/37540462/circular-rna-circ_0000119-promotes-cervical-cancer-cell-growth-and-migration-via-mir-433-3p-pak2-axis
#21
JOURNAL ARTICLE
Junxiao Zhang, Guanghua Chu, Lihua Zheng, Juandi Liu, Juxian He
The purpose of this study was to investigate the role of circ_0000119 on CC progression and its molecular mechanism. The expression levels of circ_0000119, miR-433-3p, and p21-activated kinase 2 (PAK2) in CC tissues and cell lines were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was assessed using 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay and colony formation assay. Cell cycle and apoptosis were assessed by flow cytometry...
August 4, 2023: Journal of Applied Genetics
https://read.qxmd.com/read/37397923/role-of-activated-p21-activated-kinase-2-in-methylmercury-induced-embryotoxic-effects-on-mouse-blastocysts
#22
JOURNAL ARTICLE
Cheng-Kai Lee, Fu-Ting Wang, Chien-Hsun Huang, Wen-Hsiung Chan
Methylmercury (MeHg), a biotransformation product derived from mercury or inorganic mercury compounds in waterways, is a potent toxin that exerts hazardous effects on human health via environmental contamination. Previous studies have reported MeHg-induced impairment of nerve development in embryogenesis and placental development. However, the potential deleterious effects and regulatory mechanisms of action of MeHg on pre- and post-implantation embryo development are yet to be established. Experiments from the current study clearly demonstrate that MeHg exerts toxic effects on early embryonic development processes, including the zygote to blastocyst stage...
June 2023: Toxicology Research
https://read.qxmd.com/read/37316799/the-rac-inhibitor-hv-107-as-a-potential-therapeutic-for-metastatic-breast-cancer
#23
JOURNAL ARTICLE
Grace Velez Crespo, Jescelica Ortiz, Eliud Hernández O'Farrill, Cornelis P Vlaar, Mikhail Inyushin, Yuriy Kucheryavykh, Lilia Kucheryavykh
BACKGROUND: The significant challenge in treating triple-negative breast cancer (TNBC) lies in its high rate of distant metastasis. To address this, inhibiting metastasis formation in TNBC is vital. Rac is a key player in cancer metastasis. Previously, we developed Ehop-016, a Rac inhibitor that successfully reduced tumor growth and metastasis in mice. In this study, we assessed the effectiveness of HV-107, a derivative of Ehop-016, in inhibiting TNBC metastasis at lower doses. METHODS: Rho GTPases activity assays were performed with the use of GST-PAK beads and Rac, Rho, and Cdc42 GLISA...
June 14, 2023: Molecular Medicine
https://read.qxmd.com/read/37306572/lncrna-pcbp1-as1-induces-osteoporosis-by-sponging-mir-126-5p-pak2-axis
#24
JOURNAL ARTICLE
Zhihui Li
AIMS: Long non-coding RNAs (lncRNAs) act as crucial regulators in osteoporosis (OP). Nonetheless, the effects and potential molecular mechanism of lncRNA PCBP1 Antisense RNA 1 (PCBP1-AS1) on OP remain largely unclear. The aim of this study was to explore the role of lncRNA PCBP1-AS1 in the pathogenesis of OP. METHODS: Using quantitative real-time polymerase chain reaction (qRT-PCR), osteogenesis-related genes (alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN), and Runt-related transcription factor 2 (RUNX2)), PCBP1-AS1, microRNA (miR)-126-5p, group I Pak family member p21-activated kinase 2 (PAK2), and their relative expression levels were determined...
June 12, 2023: Bone & Joint Research
https://read.qxmd.com/read/37199682/recurrent-pak2-rearrangements-in-poroma-with-folliculo-sebaceous-differentiation
#25
JOURNAL ARTICLE
Thibault Kervarrec, Daniel Pissaloux, Sandrine Paindavoine, Franck Tirode, Amélie Osio, Samia Mourah, Fanélie Jouenne, Pierre Sohier, Eduardo Calonje, Agnes Pekar, Evelyn Vanesa Erazo Luna, Keisuke Goto, Flore Delalande, Eric Frouin, Nicolas Macagno, Françoise Drouot, Monique Faisan, Bernard Cribier, Maxime Battistella, Arnaud de la Fouchardière
AIMS: Poroma is a benign adnexal neoplasm with differentiation towards the upper portion of the sweat gland apparatus. In 2019, Sekine et al. demonstrated recurrent YAP1::MAML2 and YAP1::NUTM1 fusion in poroma and porocarcinoma. Follicular, sebaceous and/or apocrine differentiation has been reported in rare cases of poroma and whether these tumours constitute a variant of poroma or represent a distinctive tumour is a matter to debate. Herein we describe the clinical, immunophenotypic, and molecular features of 13 cases of poroma with folliculo-sebaceous differentiation...
August 2023: Histopathology
https://read.qxmd.com/read/37190165/targeting-p21-activated-kinase-1-for-metastatic-prostate-cancer
#26
REVIEW
Payaningal R Somanath, Jonathan Chernoff, Brian S Cummings, Sandip M Prasad, Harvey D Homan
Metastatic prostate cancer (mPCa) has limited therapeutic options and a high mortality rate. The p21-activated kinase (PAK) family of proteins is important in cell survival, proliferation, and motility in physiology, and pathologies such as infectious, inflammatory, vascular, and neurological diseases as well as cancers. Group-I PAKs (PAK1, PAK2, and PAK3) are involved in the regulation of actin dynamics and thus are integral for cell morphology, adhesion to the extracellular matrix, and cell motility. They also play prominent roles in cell survival and proliferation...
April 11, 2023: Cancers
https://read.qxmd.com/read/37124501/comparative-analysis-between-high-grade-serous-ovarian-cancer-and-healthy-ovarian-tissues-using-single-cell-rna-sequencing
#27
JOURNAL ARTICLE
Xiao Zhang, Shihao Hong, Chengying Yu, Xiaozhong Shen, Fangying Sun, Jianhua Yang
INTRODUCTION: High-grade serous ovarian cancer (HGSOC) is the most common histological subtype of ovarian cancer, and is associated with high mortality rates. METHODS: In this study, we analyzed specific cell subpopulations and compared different gene functions between healthy ovarian and ovarian cancer cells using single-cell RNA sequencing (ScRNA-seq). We delved deeper into the differences between healthy ovarian and ovarian cancer cells at different levels, and performed specific analysis on endothelial cells...
2023: Frontiers in Oncology
https://read.qxmd.com/read/36869386/subtype-specific-kinase-dependency-regulates-growth-and-metastasis-of-poor-prognosis-mesenchymal-colorectal-cancer
#28
JOURNAL ARTICLE
Joyce Y Buikhuisen, Patricia M Gomez Barila, Kate Cameron, Saskia J E Suijkerbuijk, Cor Lieftink, Simone di Franco, Ana Krotenberg Garcia, Rebeca Uceda Castro, Kristiaan J Lenos, Lisanne E Nijman, Arezo Torang, Ciro Longobardi, Joan H de Jong, Daniëlle Dekker, Giorgio Stassi, Louis Vermeulen, Roderick L Beijersbergen, Jacco van Rheenen, Stephan Huveneers, Jan Paul Medema
BACKGROUND: Colorectal cancer (CRC) can be divided into four consensus molecular subtypes (CMS), each with distinct biological features. CMS4 is associated with epithelial-mesenchymal transition and stromal infiltration (Guinney et al., Nat Med 21:1350-6, 2015; Linnekamp et al., Cell Death Differ 25:616-33, 2018), whereas clinically it is characterized by lower responses to adjuvant therapy, higher incidence of metastatic spreading and hence dismal prognosis (Buikhuisen et al., Oncogenesis 9:66, 2020)...
March 3, 2023: Journal of Experimental & Clinical Cancer Research: CR
https://read.qxmd.com/read/36825780/myosin-ii-regulatory-light-chain-phosphorylation-and-formin-availability-modulate-cytokinesis-upon-changes-in-carbohydrate-metabolism
#29
JOURNAL ARTICLE
Francisco Prieto-Ruiz, Elisa Gómez-Gil, Rebeca Martín-García, Armando Jesus Perez-Diaz, Jero Vicente-Soler, Alejandro Franco, Teresa Soto, Pilar Pérez, Marisa Madrid, Jose Cansado
Cytokinesis, the separation of daughter cells at the end of mitosis, relies in animal cells on a contractile actomyosin ring (CAR) composed of actin and class II myosins, whose activity is strongly influenced by regulatory light chain (RLC) phosphorylation. However, in simple eukaryotes such as the fission yeast Schizosaccharomyces pombe , RLC phosphorylation appears dispensable for regulating CAR dynamics. We found that redundant phosphorylation at Ser35 of the S. pombe RLC homolog Rlc1 by the p21-activated kinases Pak1 and Pak2, modulates myosin II Myo2 activity and becomes essential for cytokinesis and cell growth during respiration...
February 24, 2023: ELife
https://read.qxmd.com/read/36813765/pak2-is-essential-for-chromosome-alignment-in-metaphase-i-oocytes
#30
JOURNAL ARTICLE
Juan Zeng, Shiwei Wang, Min Gao, Dian Lu, Shuang Song, Diyu Chen, Weimin Fan, Zhiliang Xu, Zhiguo Zhang, Xiaofang Sun
As a highly conserved and ubiquitously expressed serine/threonine kinase, p21-activated kinase 2 (PAK2) participates in diverse biologic events. However, its roles in mouse oocyte meiotic maturation remain unclear. The present study revealed that mouse oocytes depleted of Pak2 were unable to completely progress through meiosis and that a majority were arrested at metaphase I. Pak2 depletion thus prompted MI arrest and induced meiotic chromosome alignment defects in mouse oocytes, in part due to a reduction in polo-like kinase (PLK1)...
February 22, 2023: Cell Death & Disease
https://read.qxmd.com/read/36775351/p21-activated-kinase-2-binds-to-transcription-factor-sox2-and-up-regulates-dek-to-promote-the-progression-of-lung-squamous-cell-carcinoma
#31
JOURNAL ARTICLE
Shiguang Xie, Xuan Wan, Shuyun Chen, Yan Hu, Xiaoming Liu
Lung squamous cell carcinoma (LSCC) is a prevalent and progressive subtype of lung cancer. This study aimed to substantiate the regulatory effect of the PAK2/SOX2/DEK axis on the LSCC development. LSCC tissues (n = 83) and adjacent normal tissues were collected and SOX2 expression was determined by qRT-PCR and Western blotting. Correlation between SOX2 expression and the prognosis of LSCC patients was then explored utilizing Kaplan-Meier analysis. Co-immunoprecipitation and glutathione-S-transferase pull-down assays were conducted to validate the binding of SOX2 to DEK...
October 2022: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://read.qxmd.com/read/36747819/cross-species-transcriptomic-analysis-identifies-mitochondrial-dysregulation-as-a-functional-consequence-of-the-schizophrenia-associated-3q29-deletion
#32
Ryan H Purcell, Esra Sefik, Erica Werner, Alexia T King, Trenell J Mosley, Megan E Merritt-Garza, Pankaj Chopra, Zachary T McEachin, Sridhar Karne, Nisha Raj, Kedamawit Tilahun, Maxine Robinette, Stephen T Warren, Zhexing Wen, Victor Faundez, Steven A Sloan, Gary J Bassell, Jennifer G Mulle
Recent advances in the genetics of schizophrenia (SCZ) have identified rare variants that confer high disease risk, including a 1.6 Mb deletion at chromosome 3q29 with a staggeringly large effect size (O.R. > 40). Understanding the impact of the 3q29 deletion (3q29Del) on the developing CNS may therefore lead to insights about the pathobiology of schizophrenia. To gain clues about the molecular and cellular perturbations caused by the 3q29 deletion, we interrogated transcriptomic effects in two experimental model systems with complementary advantages: isogenic human forebrain cortical organoids and isocortex from the 3q29Del mouse model...
January 28, 2023: bioRxiv
https://read.qxmd.com/read/36740679/circular-rna-0001789-sponges-mir-140-3p-and-regulates-pak2-to-promote-the-progression-of-gastric-cancer
#33
JOURNAL ARTICLE
Jun You, Yinan Chen, Donghan Chen, Yongwen Li, Tinghao Wang, Jingtao Zhu, Qingqi Hong, Qiyuan Li
BACKGROUND: Gastric cancer (GC) is the third-leading cause of cancer-associated mortalities globally. The deregulation of circular RNAs (circRNAs) and microRNAs (miRNAs or miRs) is widely implicated in the pathogenesis and progression of different cancer types. METHODS: The expression profiling of circRNAs in GC is required to identify crucial circRNAs as biomarkers or therapeutic targets. In the present study, a published circRNA microarray dataset was used to identify differentially expressed circRNAs between GC tissues and normal gastric mucosa tissues...
February 5, 2023: Journal of Translational Medicine
https://read.qxmd.com/read/36696687/peptide-protein-coassemblies-into-hierarchical-and-bioactive-tubular-membranes
#34
JOURNAL ARTICLE
Anna Majkowska, Karla E Inostroza-Brito, Mariel Gonzalez, Carlos Redondo-Gómez, Alistair Rice, Jose Carlos Rodriguez-Cabello, Armando E Del Rio Hernandez, Alvaro Mata
Multicomponent self-assembly offers opportunities for the design of complex and functional biomaterials with tunable properties. Here, we demonstrate how minor modifications in the molecular structures of peptide amphiphiles (PAs) and elastin-like recombinamers (ELs) can be used to generate coassembling tubular membranes with distinct structures, properties, and bioactivity. First, by introducing minor modifications in the charge density of PA molecules (PAK2, PAK3, PAK4), different diffusion-reaction processes can be triggered, resulting in distinct membrane microstructures...
January 25, 2023: Biomacromolecules
https://read.qxmd.com/read/36671485/mechanism-by-which-pf-3758309-a-pan-isoform-inhibitor-of-p21-activated-kinases-blocks-reactivation-of-hiv-1-latency
#35
JOURNAL ARTICLE
Benni Vargas, James Boslett, Nathan Yates, Nicolas Sluis-Cremer
The "block and lock" strategy is one approach that might elicit a sterilizing cure for HIV-1 infection. The "block" refers to a compound's ability to inhibit latent HIV-1 proviral transcription, while the "lock" refers to its capacity to induce permanent proviral silencing. We previously identified PF-3758309, a pan-isoform inhibitor of p21-activated kinases (PAKs), as a potent inhibitor of HIV-1 latency reversal. The goal of this study was to define the mechanism(s) involved. We found that both 24ST1NLESG cells (a cell line model of HIV-1 latency) and purified CD4+ naïve and central memory T cells express high levels of PAK2 and lower levels of PAK1 and PAK4...
January 4, 2023: Biomolecules
https://read.qxmd.com/read/36622146/ap-2-adaptor-complex-dependent-enhancement-of-hiv-1-replication-by-nef-in-the-absence-of-the-nef-ap-2-targets-serinc5-and-cd4
#36
JOURNAL ARTICLE
Balaji Olety, Yoshiko Usami, Yuanfei Wu, Paul Peters, Heinrich Göttlinger
Human immunodeficiency virus type 1 (HIV-1) Nef hijacks the clathrin adaptor complex 2 (AP-2) to downregulate the viral receptor CD4 and the antiviral multipass transmembrane proteins SERINC3 and SERINC5, which inhibit the infectivity of progeny virions when incorporated. In Jurkat Tag T lymphoid cells lacking SERINC3 and SERINC5, Nef is no longer required for full progeny virus infectivity and for efficient viral replication. However, in MOLT-3 T lymphoid cells, HIV-1 replication remains highly dependent on Nef even in the absence of SERINC3 and SERINC5...
January 9, 2023: MBio
https://read.qxmd.com/read/36594092/neutrophil-extracellular-traps-delay-diabetic-wound-healing-by-inducing-endothelial-to-mesenchymal-transition-via-the-hippo-pathway
#37
JOURNAL ARTICLE
Shuofei Yang, ShuangShuang Wang, Liang Chen, Zheyu Wang, Jiaquan Chen, Qihong Ni, Xiangjiang Guo, Lan Zhang, Guanhua Xue
Diabetic foot ulcers (DFUs) are among the most frequent complications of diabetes with significant morbidity and mortality. Diabetes can trigger neutrophils to undergo histone citrullination by protein arginine deiminase 4 (encoded by Padi4 in mice) and release neutrophil extracellular traps (NETs). The specific mechanism of NETs-mediated wound healing impairment in diabetes remains unknown. In this study, we show neutrophils are more susceptible to NETosis in diabetic wound environments. Via in vitro experiments and in vivo models of wound healing using wide-type and Padi4 -/- mice, we demonstrate NETs can induce the activation of PAK2 via the membrane receptor TLR-9...
2023: International Journal of Biological Sciences
https://read.qxmd.com/read/36564030/proximity-proteomics-identifies-septin-and-pak2-as-decisive-regulators-of-actomyosin-expulsion-of-von-willebrand-factor
#38
JOURNAL ARTICLE
Sammy El-Mansi, Christopher L Robinson, Katja B Kostelnik, Jessica J McCormack, Tom P Mitchell, Damián Lobato-Márquez, Vinothini Rajeeve, Pedro R Cutillas, Daniel F Cutler, Serge Mostowy, Thomas D Nightingale
In response to tissue injury, within seconds the ultra large glycoprotein, von Willebrand factor (VWF) is released from endothelial storage organelles (Weibel-Palade bodies) into the lumen of the blood vasculature where it leads to the recruitment of platelets. The marked size of VWF multimers represents an unprecedented burden on the secretory machinery of endothelial cells (ECs). ECs have evolved mechanisms to overcome this, most notably an actomyosin ring, that forms, contracts and squeezes out its unwieldy cargo...
December 23, 2022: Blood
https://read.qxmd.com/read/36504449/loss-of-function-of-p21-activated-kinase-2-links-bmp-signaling-to-neural-tube-patterning-defects
#39
JOURNAL ARTICLE
Yan Wang, Kaifan Zhang, Jin Guo, Shuyan Yang, Xiaohui Shi, Jinrong Pan, Zheng Sun, Jizhen Zou, Yi Li, Yuanyuan Li, Tianda Fan, Wei Song, Fang Cheng, Cheng Zeng, Jinchen Li, Ting Zhang, Zhong Sheng Sun
Closure of the neural tube represents a highly complex and coordinated process, the failure of which constitutes common birth defects. The serine/threonine kinase p21-activated kinase 2 (PAK2) is a critical regulator of cytoskeleton dynamics; however, its role in the neurulation and pathogenesis of neural tube defects (NTDs) remains unclear. Here, the results show that Pak2-/- mouse embryos fail to develop dorsolateral hinge points (DLHPs) and exhibit craniorachischisis, a severe phenotype of NTDs. Pak2 knockout activates BMP signaling that involves in vertebrate bone formation...
December 11, 2022: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://read.qxmd.com/read/36416208/development-and-utility-of-a-pak1-selective-degrader
#40
JOURNAL ARTICLE
Hoi-Yee Chow, Sofiia Karchugina, Brian J Groendyke, Sean Toenjes, John Hatcher, Katherine A Donovan, Eric S Fischer, Gleb Abalakov, Bulat Faezov, Roland Dunbrack, Nathanael S Gray, Jonathan Chernoff
Overexpression of PAK1, a druggable kinase, is common in several malignancies, and inhibition of PAK1 by small molecules has been shown to impede the growth and survival of such cells. Potent inhibitors of PAKs 1-3 have been described, but clinical development has been hindered by recent findings that PAK2 function is required for normal cardiovascular function in adult mice. A unique allosteric PAK1-selective inhibitor, NVS-PAK1-1, provides a potential path forward, but has modest potency. Here, we report the development of BJG-05-039, a PAK1-selective degrader consisting of NVS-PAK1-1 conjugated to lenalidomide, a recruiter of the E3 ubiquitin ligase substrate adaptor Cereblon...
November 23, 2022: Journal of Medicinal Chemistry
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