MICAL2 Facilitates Gastric Cancer Cell Migration via MRTF-A-Mediated CDC42 Activation

Wang, Yueyuan; Min, Pengxiang; Qi, Chenxiang; Zhao, Shuo; Yu, Min-Jie; Zhang, Yujie; Du, Jie

doi:10.3389/fmolb.2021.568868

Cited by 9 publications

(10 citation statements)

References 37 publications

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“…Of note, MICAL1 exerts its effect on proliferation via reactive oxygen species (ROS)-sensitive PI3K/AKT/ERK signaling in breast cancer cells [ 33 ]. Similarly, MICAL2-induced ROS generation has also been reported to enhance the migratory potential of gastric cancer cells [ 34 ]. MICAL-L2 lacks the FAD domain and cannot generate ROS [ 35 ], and although several studies have suggested that MICAL-L2 may positively influence cancer progression [ 10 , 13 , 36 ], whether and how MICAL-L2 may be involved in this process remains unclear.…”

Section: Discussionmentioning

confidence: 99%

High MICAL-L2 expression and its role in the prognosis of colon adenocarcinoma

Yang

Xia

et al. 2022

BMC Cancer

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Background MICAL-like protein 2 (MICAL-L2), a member of the molecules interacting with CasL (MICAL) family of proteins, is strongly associated with the malignancy of multiple types of cancer. However, the role of MICAL-L2 in colon adenocarcinoma (COAD) has not been well characterized. Methods In this study, we analyzed the role of MICAL-L2 in COAD using datasets available from public databases. The mRNA and protein expression of MICAL-L2 was investigated using TCGA, UALCAN, and independent immunohistochemical assays. Overall survival (OS) and disease-specific survival (DSS) of COAD patients were assessed based on the MICAL-L2 expression level using the Kaplan–Meier method. Univariate and multivariate analysis was employed to determine whether MICAL-L2 could serve as an independent prognostic indicator of OS. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were further utilized to explore the possible cellular mechanism underlying the role of MICAL-L2 in COAD. In addition, the correlation between MICAL-L2 expression and immune cell infiltration levels was investigated via single-sample gene set enrichment analysis (ssGSEA). Results Data from TCGA, HPA, and UALCAN datasets indicated that MICAL-L2 expression was significantly higher in COAD tissue than in adjacent normal tissues, and this was confirmed by immunohistochemical assays. Kaplan–Meier survival analysis revealed that patients with MICAL-L2 had shorter OS and DSS. Furthermore, multivariate Cox analysis indicated that MICAL-L2 was an independent risk factor for OS in COAD patients. ROC analysis confirmed the diagnostic value of MICAL-L2, and a prognostic nomogram involving age, M stage, and MICAL-L2 expression was constructed for OS. Functional enrichment analyses revealed that transport-related activity was closely associated with the role of MICAL-L2 in COAD. Regarding immune infiltration levels, MICAL-L2 was found to be positively associated with CD56bright NK cells. Conclusions Our results suggested that MICAL-L2 is a promising biomarker for determining prognosis and correlated with immune infiltration levels in COAD.

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Section: Discussionmentioning

confidence: 99%

High MICAL-L2 expression and its role in the prognosis of colon adenocarcinoma

Yang

Xia

et al. 2022

BMC Cancer

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“…Variants of Formins also have been identified in human microcephaly patients( 23, 24, 38 ). MRTF is a downstream effector of Formin/Diaphanous-mediated actin dynamics for regulating the transcription of cell motility- and proliferation-related genes in tumor cells and fibroblasts( 87–89 ). We found that microcephaly-like phenotype in the larva carrying loss-of-function allele of dia can be suppressed by Mrtf overexpression in NSCs, suggesting that Dia-Mrtf signaling plays an important role during brain development.…”

Section: Discussionmentioning

confidence: 99%

Astrocytes control quiescent NSC reactivation via GPCR signaling-mediated F-actin remodeling

Lin,

Gujar,

Lin

et al. 2024

Preprint

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The transitioning of neural stem cells (NSCs) between quiescent and proliferative states is fundamental for brain development and homeostasis. Defects in NSC reactivation are associated with neurodevelopmental disorders.Drosophilaquiescent NSCs extend an actin-rich primary protrusion toward the neuropil. However, the function of the actin cytoskeleton during NSC reactivation is unknown. Here, we reveal the fine F-actin structures in the protrusions of quiescent NSCs by expansion and super-resolution microscopy. We show that F-actin polymerization promotes the nuclear translocation of Mrtf, a microcephaly-associated transcription factor, for NSC reactivation and brain development. F-actin polymerization is regulated by a signaling cascade composed of G-protein-coupled receptor (GPCR) Smog, G-protein αq subunit, Rho1 GTPase, and Diaphanous (Dia)/Formin during NSC reactivation. Further, astrocytes secrete a Smog ligand Fog to regulate Gαq-Rho1-Dia-mediated NSC reactivation. Together, we establish that the Smog-Gαq-Rho1 signaling axis derived from astrocytes, a NSC niche, regulates Dia-mediated F-actin dynamics in NSC reactivation.

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“…Subsequently, miR-155 suppresses the expression of SOX1 to promote gastric cancer cell migration. 511 Furthermore, Wang et al 512 showed that MICALC2-mediated upregulation of nuclear MRTF-A promotes CDC42 activation, MMP9 expression, and gastric cancer cell migration. 512 …”

Section: Diseases Associated With Mutation Of Transcription Co-activa...mentioning

confidence: 99%

“… 511 Furthermore, Wang et al 512 showed that MICALC2-mediated upregulation of nuclear MRTF-A promotes CDC42 activation, MMP9 expression, and gastric cancer cell migration. 512 …”

Section: Diseases Associated With Mutation Of Transcription Co-activa...mentioning

confidence: 99%

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Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases

Talukdar,

Chatterji

2023

Sig Transduct Target Ther

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Specific cell states in metazoans are established by the symphony of gene expression programs that necessitate intricate synergic interactions between transcription factors and the co-activators. Deregulation of these regulatory molecules is associated with cell state transitions, which in turn is accountable for diverse maladies, including developmental disorders, metabolic disorders, and most significantly, cancer. A decade back most transcription factors, the key enablers of disease development, were historically viewed as ‘undruggable’; however, in the intervening years, a wealth of literature validated that they can be targeted indirectly through transcriptional co-activators, their confederates in various physiological and molecular processes. These co-activators, along with transcription factors, have the ability to initiate and modulate transcription of diverse genes necessary for normal physiological functions, whereby, deregulation of such interactions may foster tissue-specific disease phenotype. Hence, it is essential to analyze how these co-activators modulate specific multilateral processes in coordination with other factors. The proposed review attempts to elaborate an in-depth account of the transcription co-activators, their involvement in transcription regulation, and context-specific contributions to pathophysiological conditions. This review also addresses an issue that has not been dealt with in a comprehensive manner and hopes to direct attention towards future research that will encompass patient-friendly therapeutic strategies, where drugs targeting co-activators will have enhanced benefits and reduced side effects. Additional insights into currently available therapeutic interventions and the associated constraints will eventually reveal multitudes of advanced therapeutic targets aiming for disease amelioration and good patient prognosis.

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MICAL2 Facilitates Gastric Cancer Cell Migration via MRTF-A-Mediated CDC42 Activation

Cited by 9 publications

References 37 publications

High MICAL-L2 expression and its role in the prognosis of colon adenocarcinoma

High MICAL-L2 expression and its role in the prognosis of colon adenocarcinoma

Astrocytes control quiescent NSC reactivation via GPCR signaling-mediated F-actin remodeling

Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases

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