CLDN6 inhibits breast cancer metastasis through WIP-dependent actin cytoskeleton-mediated autophagy DOI Creative Commons

Yuan Dong,

Jin Qiu,

Minghao Sun

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: March 20, 2023

Abstract Background As a breast cancer suppressor gene, CLDN6 overexpression was found to inhibit metastasis in our previous studies, but the specific mechanism remains unclear. This study aimed clarify role and of inhibiting metastasis. Methods Western blot, immunofluorescence transmission electron microscopy were performed detect autophagy. Wound healing, transwell assays lung mouse models used examine Phalloidin staining immunofluorescent observe actin cytoskeleton. mRNA seq, RT-PCR, western chromatin immunoprecipitation, dual luciferase reporter assay, co-immunoprecipitation define molecular mechanism. The expression levels clinical implication CLDN6, WIP LC3 tissues evaluated using immunohistochemistry. Results We demonstrated that inhibited through autophagy vitro vivo. unraveled novel regulated via WIP-dependent cytoskeleton assembly. Through its PDZ-binding motif, overexpressed interacted with JNK upregulated JNK/c-Jun pathway. C-Jun promoted at transcriptional level. Notably, we observed c-Jun transcriptionally expression, there positive feedback loop between JNK/c-Jun. Finally, correlated each other, significantly associated lymph node patients. Conclusions data provide new insight into inhibitory effects CLDN6-mediated on metastasis, revealed regulating Our findings enrich theoretical basis for as potential biomarker diagnosis therapy.

Language: Английский

Intrinsic Control of Axon Regeneration DOI Creative Commons
Zhigang He, Yishi Jin

Neuron, Journal Year: 2016, Volume and Issue: 90(3), P. 437 - 451

Published: May 1, 2016

Language: Английский

Citations

556
JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships DOI Open Access
András Zeke, Mariya Misheva, Attila Reményi

et al.

Microbiology and Molecular Biology Reviews, Journal Year: 2016, Volume and Issue: 80(3), P. 793 - 835

Published: July 28, 2016

SUMMARY The c-Jun N-terminal kinases (JNKs), as members of the mitogen-activated protein kinase (MAPK) family, mediate eukaryotic cell responses to a wide range abiotic and biotic stress insults. JNKs also regulate important physiological processes, including neuronal functions, immunological actions, embryonic development, via their impact on gene expression, cytoskeletal dynamics, death/survival pathways. Although JNK pathway has been under study for >20 years, its complexity is still perplexing, with multiple partners underlying diversity actions. Here we review current knowledge structure isoforms well partnerships intracellular proteins. Many these proteins are direct substrates JNKs. We analyzed almost 100 target in detail within framework classification based regulation by Examples include diverse assortment nuclear transcription factors (Jun, ATF2, Myc, Elk1), cytoplasmic involved cytoskeleton (DCX, Tau, WDR62) or vesicular transport (JIP1, JIP3), membrane receptors (BMPR2), mitochondrial (Mcl1, Bim). In addition, because upstream signaling components activity, critically assessed involvement scaffolds roles feedback mechanisms pathway. Despite clarification many regulatory events JNK-dependent during past decade, other structural mechanistic insights just beginning be revealed. These advances open new opportunities understand role pathophysiological states.

Language: Английский

Citations

442
CRISPR Interference-Based Platform for Multimodal Genetic Screens in Human iPSC-Derived Neurons DOI Creative Commons
Ruilin Tian, Mariam A. Gachechiladze, Connor H. Ludwig

et al.

Neuron, Journal Year: 2019, Volume and Issue: 104(2), P. 239 - 255.e12

Published: Aug. 15, 2019

Highlights•A CRISPR interference platform for genetic screens in human iPSC-derived neurons•Survival uncover genes essential neurons, but not iPSCs or cancer cells•Single-cell RNA-seq reveal distinct neuronal roles ubiquitous genes•Arrayed high-content controlling morphologySummaryCRISPR/Cas9-based functional genomics have transformed our ability to elucidate mammalian cell biology. However, most previous CRISPR-based were conducted lines rather than healthy, differentiated cells. Here, we describe a (CRISPRi)-based neurons derived from induced pluripotent stem cells (iPSCs). We demonstrate robust and durable knockdown of endogenous such present results three complementary screens. First, survival-based screen revealed neuron-specific that improved survival upon knockdown. Second, with single-cell transcriptomic readout uncovered several examples whose had strikingly cell-type-specific consequences. Third, longitudinal imaging detected consequences gene on morphology. Our highlight the power unbiased types provide systematic interrogation normal disease states neurons.Video Abstract/cms/asset/c2672569-5397-4e97-a52a-74b50c33ac04/mmc10.mp4Loading ...Download video (mp4, 134 MB)Graphical abstract

Language: Английский

Citations

415
Axon Self-Destruction: New Links among SARM1, MAPKs, and NAD+ Metabolism DOI Creative Commons

Josiah Gerdts,

Daniel W. Summers, Jeffrey Milbrandt

et al.

Neuron, Journal Year: 2016, Volume and Issue: 89(3), P. 449 - 460

Published: Feb. 1, 2016

Language: Английский

Citations

311
Axon–soma communication in neuronal injury DOI
Ida Rishal, Mike Fainzilber

Nature reviews. Neuroscience, Journal Year: 2013, Volume and Issue: 15(1), P. 32 - 42

Published: Dec. 11, 2013

Language: Английский

Citations

276
Alzheimer’s-associated PLCγ2 is a signaling node required for both TREM2 function and the inflammatory response in human microglia DOI

Benjamin J. Andreone,

Laralynne Przybyla,

Ceyda Llapashtica

et al.

Nature Neuroscience, Journal Year: 2020, Volume and Issue: 23(8), P. 927 - 938

Published: June 8, 2020

Language: Английский

Citations

193
BAX to basics: How the BCL2 gene family controls the death of retinal ganglion cells DOI
Margaret E. Maes,

Cassandra L. Schlamp,

Robert W. Nickells

et al.

Progress in Retinal and Eye Research, Journal Year: 2017, Volume and Issue: 57, P. 1 - 25

Published: Jan. 5, 2017

Language: Английский

Citations

177
Apoptotic cell death regulation in neurons DOI Open Access
Émilie Hollville, Selena E. Romero, Mohanish Deshmukh

et al.

FEBS Journal, Journal Year: 2019, Volume and Issue: 286(17), P. 3276 - 3298

Published: June 23, 2019

Apoptosis plays a major role in shaping the developing nervous system during embryogenesis as neuronal precursors differentiate to become post‐mitotic neurons. However, once neurons are incorporated into functional circuits and mature, they greatly restrict their capacity die via apoptosis, thus allowing mature persist healthy state throughout life. This robust restriction of apoptotic pathway differentiation maturation is defined by multiple unique mechanisms that function more precisely control intrinsic pathway. while these necessary for survival, still capable activating certain pathological contexts. In this review, we highlight key governing survival neurons, also detailing physiological contexts which overcoming high threshold.

Language: Английский

Citations

170
MAPK-Activated Protein Kinases: Servant or Partner? DOI Open Access
Natalia Ronkina, Matthias Gaestel

Annual Review of Biochemistry, Journal Year: 2022, Volume and Issue: 91(1), P. 505 - 540

Published: March 19, 2022

Mitogen-activated protein kinase (MAPK)-activated kinases (MAPKAPKs) are defined by their exclusive activation MAPKs. They can be activated classical and atypical MAPKs that have been stimulated mitogens various stresses. Genetic deletions of MAPKAPKs availability highly specific small-molecule inhibitors continuously increased our functional understanding these kinases. cooperate in the regulation gene expression at level transcription; RNA processing, export, stability; synthesis. The diversity stimuli for MAPK activation, crosstalk between different MAPKAPKs, substrate pattern orchestrate immediate-early inflammatory responses space time ensure proper control cell growth, differentiation, behavior. Hence, promising targets cancer therapy treatments conditions acute chronic inflammation, such as cytokine storms rheumatoid arthritis.

Language: Английский

Citations

99
The Role of the Dysregulated JNK Signaling Pathway in the Pathogenesis of Human Diseases and Its Potential Therapeutic Strategies: A Comprehensive Review DOI Creative Commons

Huaying Yan,

Lanfang He,

De Lv

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(2), P. 243 - 243

Published: Feb. 19, 2024

JNK is named after c-Jun N-terminal kinase, as it responsible for phosphorylating c-Jun. As a member of the mitogen-activated protein kinase (MAPK) family, also known stress-activated (SAPK) because can be activated by extracellular stresses including growth factor, UV irradiation, and virus infection. Functionally, regulates various cell behaviors such differentiation, proliferation, survival, metabolic reprogramming. Dysregulated signaling contributes to several types human diseases. Although role pathway in single disease has been summarized previous publications, comprehensive review its multiple kinds diseases missing. In this review, we begin introducing landmark discoveries, structures, tissue expression, activation mechanisms pathway. Next, come focus work: summary deregulated Beyond that, discuss current strategies targeting therapeutic intervention summarize application inhibitors well challenges now faced. We expect that provide more insight into critical pathogenesis hope provides important clues ameliorating conditions.

Language: Английский

Citations

33