Rac1: A Regulator of Cell Migration and a Potential Target for Cancer Therapy

Ma, Ning; Xu, Erqian; Luo, Qing; Song, Guanbin

doi:10.3390/molecules28072976

Cited by 16 publications

(4 citation statements)

References 119 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Single-cell sequencing technology 42,43 has shown great potential in the study of the tumour microenvironment, providing a new perspective for the diagnosis, treatment, and prognosis of cancer 44 . The ability of RAC1 to promote the proliferation and migration of various tumour cell has been confirmed 6,7,31,45 , but there is currently a lack of research on the precise expression distribution and function of RAC1 in the tumour microenvironment. A study employing single-cell RNA sequencing has uncovered a marked upregulation of RAC1 in lung adenocarcinoma brain metastasis, elucidating its pivotal role in this process 8 .…”

Section: Discussionmentioning

confidence: 99%

“…Rac1 is commonly characterized by its heightened expression and/or enhanced activity in a spectrum of solid malignancies, such as bladder 5 , and hepatocellular carcinomas 6 . At the same time, RAC1 is also closely related to tumour metastasis 7 . In lung cancer, a study has indicated that RAC1 is highly expressed in circulating tumours cells and lung metastatic cells, suggesting its role in metastasis 8 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Integrated Pan-Cancer Profiling of RAC1: Prognostic, Immunomodulatory, and Therapeutic Resistance Insights

Shao,

Ren,

Wang

et al. 2024

Preprint

View full text Add to dashboard Cite

RAC1, a member of the Rho family GTPases, has been implicated in various cancer types, but its pan-cancer landscape and clinical significance remain underexplored. In this study, we conducted a comprehensive analysis of RAC1 expression, its correlation with clinical outcomes, and its role in the tumour microenvironment across 33 cancer types. Our findings revealed that RAC1 is highly expressed in a broad range of cancers and is associated with poor prognosis. RAC1 expression was found to be significantly linked to genomic alterations, including copy number variations (CNVs), tumour mutational burden (TMB), and microsatellite instability (MSI). Moreover, RAC1 was negatively correlated with B cell infiltration, suggesting its potential role in shaping a "cold" tumour microenvironment. Functional enrichment analysis indicated that RAC1 is involved in pathways related to B cell activation and immune response. Loss-of-function experiments demonstrated that RAC1 knockdown reduces cell proliferation in breast and lung cancer cells, in vivo and in vitro, suggesting its oncogenic potential. Single-cell analysis uncovered that RAC1 predominantly exerts its influence within epithelial cells. This pan-cancer analysis provides a detailed understanding of RAC1's role in cancer progression and its potential as a prognostic biomarker and therapeutic target for immunotherapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Integrated Pan-Cancer Profiling of RAC1: Prognostic, Immunomodulatory, and Therapeutic Resistance Insights

Shao,

Ren,

Wang

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Conversely, cell migration refers to the movement of cells themselves, and the mechanical properties of actively migrating cells are believed to be determined by the cytoskeletal network [43]. The FAK/Src/Cas/Rho GTPase signaling pathway controls cell migration by modulating the cytoskeleton [44]. The coordinated assembly and breakdown of actin filaments provide the primary energy source for cell migration, and the Rho family GTPases Cdc42, Rac1, and RhoA are essential components of this process [45].…”

Section: Discussionmentioning

confidence: 99%

Cellular Functions of High-Temperature Requirement Factor A4 in Placenta

Pei

Choi

Park

et al. 2023

Cells

View full text Add to dashboard Cite

The expression of High-temperature requirement factor A4 (HtrA4) mRNA is significantly lower in the chorionic villi of patients with recurrent pregnancy loss (RPL) than in the control group. We conducted an investigation into the cellular functions of HtrA4 using the CRISPR/Cas9 system and shRNA-HtrA4 to create knockout BeWo cells and HtrA4 knockdown JEG3 cells. Our results indicated that the knockout BeWo cells exhibited reduced capacity for invasion and fusion, but increased levels of proliferation and migration, with a significantly shortened cell cycle compared to wild-type cells. Wild-type BeWo cells highly expressed cell invasion- and fusion-related factors, while knockout BeWo cells highly expressed migration-, proliferation-, and cell cycle-related factors. The shRNA-HtrA4 JEG3 cells showed a decreased capacity for invasion, but an increased capacity for migration, accompanied by a decrease in the expression of cell invasion-related factors and an increase in migration-related factors. Moreover, our ELISA results revealed that the serum HtrA4 level was lower in patients with RPL than in the controls. These findings suggest that HtrA4 depletion may be associated with placental dysfunction.

show abstract

“…The arrangement of cytoskeletal micro laments has been shown to affect cellular signal transduction [13,14] . To investigate this further, we observed cell morphology using Wright-Giemsa staining.…”

Section: The Cytoskeleton Of Oating Hhfmscs Oct4 Was Remodelledmentioning

confidence: 99%

ZO-1 remodels the cytoskeleton and boosts self-renewal in OCT4-reprogrammed human hair follicle mesenchymal stem cells through adherens junction pathway

Huang,

Ruan,

Sun

et al. 2024

Preprint

View full text Add to dashboard Cite

Background: The challenge of expanding haematopoietic stem/progenitor cells (HSPCs) in vitro has limited the clinical application of this technology. Human hair follicle mesenchymal stem cells (hHFMSCs) can be reprogrammed to generate intermediate stem cells by introducing only OCT4 (hHFMSCsOCT4). Prestimulating these cells with a low concentration of the cytokines FLT3 and SCF leads to the generation of a distinct subset, named floating hHFMSCsOCT4, which can maintain self-renewal in vitro and be induced to undergo erythropoiesis, suggesting that these cells are promising seed cells for artificial haematopoiesis. Methods: Floating cell subsets were isolated from adherent cell subsets using centrifugation. Cell adhesion was assessed through disassociation and adhesion assays. OCT4 expression levels were measured using immunofluorescence staining, RT-qPCR, and Western blotting. RNA sequencing and Gene Ontology (GO) enrichment analysis were then conducted to identify proliferation-related biological processes enriched by the upregulated differentially expressed genes (DEGs). Proliferative capacity was assessed using CCK-8 and colony formation assays. Cytoskeleton was observed through Wright‒Giemsa, Coomassie brilliant blue, and phalloidin staining. Expression of adherens junction (AJ) core members was confirmed through RT‒qPCR, Western blotting, and immunofluorescence staining before and after ZO-1 knockdown. A regulatory network was constructed to determine relationships among cytoskeleton, proliferation, and the AJ pathway. Student's t tests (GraphPad Prism 8.0.2) were used for group comparisons. The results were considered significant at P < 0.05. Results: Excessive OCT4 expression weakens adhesion and causes floating hHFMSCsOCT4. These cells have moderate proliferation and undergo cytoskeleton remodeling, with increased contraction and aggregation of F-actin near the nucleus. The upregulation of ZO-1 can impact the actin, E-cadherin, and β-catenin genes, as well as the nuclear positioning of β-catenin, leading to variations in the cytoskeleton and cell cycle. Finally, a regulatory network revealed that the AJ pathway critically bridges cytoskeletal remodelling and haematopoiesis-related proliferation in a β-catenin-dependent manner. Conclusions: Increasing OCT4 levels can remodel the cytoskeleton through the ZO-1-containing AJ pathway, potentially boosting the self-renewal ability of hHFMSCs to mimic HSPCs, suggesting a plausible mechanism for utilizing novel seed cells in artificial hematopoietic in vitro.

show abstract

Rac1: A Regulator of Cell Migration and a Potential Target for Cancer Therapy

Cited by 16 publications

References 119 publications

Integrated Pan-Cancer Profiling of RAC1: Prognostic, Immunomodulatory, and Therapeutic Resistance Insights

Integrated Pan-Cancer Profiling of RAC1: Prognostic, Immunomodulatory, and Therapeutic Resistance Insights

Cellular Functions of High-Temperature Requirement Factor A4 in Placenta

ZO-1 remodels the cytoskeleton and boosts self-renewal in OCT4-reprogrammed human hair follicle mesenchymal stem cells through adherens junction pathway

Contact Info

Product

Resources

About