Abstract PS18-30: Loss of NF1 leads to rho GTPase activation and sensitivity to multiple agents in breast cancer

2021 ◽  
Author(s):  
Melody A. Cobleigh ◽  
Matthew Najor ◽  
Satnam Brar ◽  
Sanja Turturro ◽  
Liam Portt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Rho Gtpase ◽  
Multiple Agents ◽  
Gtpase Activation

scholarly journals Long non-coding RNA ARHGAP5-AS1 inhibits migration of breast cancer cell via stabilizing SMAD7 protein

2021 ◽  
Author(s):  
Chen-Long Wang ◽  
Jing-Chi Li ◽  
Ci-Xiang Zhou ◽  
Cheng-Ning Ma ◽  
Di-Fei Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Rho Gtpase ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Breast Cancer Cell Lines ◽  
Smad7 Protein

Abstract Purpose Tumor metastasis is the main cause of death from breast cancer patients and cell migration plays a critical role in cancer metastasis. Recent studies have shown long non-coding RNAs (lncRNAs) play an essential role in the initiation and progression of cancer. In the present study, the role of an LncRNA, Rho GTPase Activating Protein 5- Antisense 1 (ARHGAP5-AS1) in breast cancer was investigated. Methods RNA sequencing was performed to find out dysregulated LncRNAs in MDA-MB-231-LM2 cells. Transwell migration assays and F-actin staining were utilized to estimate cell migration ability. RNA pulldown assays and RNA immunoprecipitation were used to prove the interaction between ARHGAP5-AS1 and SMAD7. Western blot and immunofluorescence imaging were used to examine the protein levels. Dual luciferase reporter assays were performed to evaluate the activation of TGF-β signaling. Results We analyzed the RNA-seq data of MDA-MB-231 and its highly metastatic derivative MDA-MB-231-LM2 cell lines (referred to as LM2) and identified a novel lncRNA (NR_027263) named as ARHGAP5-AS1, which expression was significantly downregulated in LM2 cells. Further functional investigation showed ARHGAP5-AS1 could inhibit cell migration via suppression of stress fibers in breast cancer cell lines. Afterwards, SMAD7 was further identified to interact with ARHGAP5-AS1 by its PY motif and thus its ubiquitination and degradation was blocked due to reduced interaction with E3 ligase SMURF1 and SMURF2. Moreover, ARHGAP5-AS1 could inhibit TGF-β signaling pathway due to its inhibitory role on SMAD7. Conclusion ARHGAP5-AS1 inhibits breast cancer cell migration via stabilization of SMAD7 protein and could serve as a novel biomarker and a potential target for breast cancer in the future.

scholarly journals Chronic lymphocytic leukemia cells induce defective LFA-1–directed T-cell motility by altering Rho GTPase signaling that is reversible with lenalidomide

Blood ◽  
2013 ◽  
Vol 121 (14) ◽  
pp. 2704-2714 ◽  
Author(s):  
Alan G. Ramsay ◽  
Rachel Evans ◽  
Shahryar Kiaii ◽  
Lena Svensson ◽  
Nancy Hogg ◽  
...  
Keyword(s):  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Cell Motility ◽  
Rho Gtpase ◽  
Lymphocytic Leukemia ◽  
Leukemia Cells ◽  
Key Points ◽  
Gtpase Activation ◽  
Activation Signaling

Key Points CLL cells induce defects in T-cell LFA-1–mediated migration by altering Rho GTPase activation signaling, downregulating RhoA and Rac1, and upregulating Cdc42. Lenalidomide repairs these T-cell defects by restoring normal Rho GTPase activation signaling.

scholarly journals Rho-GTPase activating-protein 18: a biomarker associated with good prognosis in invasive breast cancer

2017 ◽  
Vol 117 (8) ◽  
pp. 1176-1184 ◽  
Author(s):  
Mohammed A Aleskandarany ◽  
Sultan Sonbul ◽  
Rachel Surridge ◽  
Abhik Mukherjee ◽  
Carlos Caldas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Invasive Breast Cancer ◽  
Rho Gtpase ◽  
Good Prognosis ◽  
Gtpase Activating Protein

scholarly journals Impaired Rho GTPase activation abrogates cell polarization and migration in macrophages with defective lipolysis

2011 ◽  
Vol 68 (23) ◽  
pp. 3933-3947 ◽  
Author(s):  
Elma Aflaki ◽  
Nariman A. B. Balenga ◽  
Petra Luschnig-Schratl ◽  
Heimo Wolinski ◽  
Silvia Povoden ◽  
...  
Keyword(s):  
Rho Gtpase ◽  
Cell Polarization ◽  
Gtpase Activation ◽  
And Migration

scholarly journals Histone deacetylase 6-mediated deacetylation of α-tubulin coordinates cytoskeletal and signaling events during platelet activation

2013 ◽  
Vol 305 (12) ◽  
pp. C1230-C1239 ◽  
Author(s):  
Joseph E. Aslan ◽  
Kevin G. Phillips ◽  
Laura D. Healy ◽  
Asako Itakura ◽  
Jiaqing Pang ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Rho Gtpase ◽  
Specific Inhibitor ◽  
Covalent Modification ◽  
Histone Deacetylase 6 ◽  
Signaling Systems ◽  
Glycoprotein Vi ◽  
Marginal Band ◽  
Signaling Events ◽  
Gtpase Activation

The tubulin cytoskeleton plays a key role in maintaining the characteristic quiescent discoid shape of resting platelets. Upon activation, platelets undergo a dramatic change in shape; however, little is known of how the microtubule system contributes to regulating platelet shape and function. Here we investigated the role of the covalent modification of α-tubulin by acetylation in the regulation of platelet physiology during activation. Superresolution microscopy analysis of the platelet tubulin cytoskeleton showed that the marginal band together with an interconnected web of finer tubulin structures collapsed upon platelet activation with the glycoprotein VI (GPVI)-agonist collagen-related peptide (CRP). Western blot analysis revealed that α-tubulin was acetylated in resting platelets and deacetylated during platelet activation. Tubacin, a specific inhibitor of the tubulin deacetylase HDAC6, prevented tubulin deacetylation upon platelet activation with CRP. Inhibition of HDAC6 upregulated tubulin acetylation and disrupted the organization of the platelet microtubule marginal band without significantly affecting platelet volume changes in response to CRP stimulation. HDAC6 inhibitors also inhibited platelet aggregation in response to CRP and blocked platelet signaling events upstream of platelet Rho GTPase activation. Together, these findings support a role for acetylation signaling in controlling the resting structure of the platelet tubulin marginal band as well as in the coordination of signaling systems that drive platelet cytoskeletal changes and aggregation.

scholarly journals Localized Rho GTPase Activation Regulates RNA Dynamics and Compartmentalization in Tumor Cell Protrusions

2008 ◽  
Vol 283 (50) ◽  
pp. 34785-34795 ◽  
Author(s):  
Heather C. Stuart ◽  
Zongjian Jia ◽  
Anat Messenberg ◽  
Bharat Joshi ◽  
T. Michael Underhill ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Rho Gtpase ◽  
Rna Dynamics ◽  
Gtpase Activation

scholarly journals Differential expression of Rho GTPase-activating protein 20 in cancers of the breast.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
Survival Data ◽  
Rho Gtpase ◽  
Differentially Expressed Gene ◽  
Normal Breast ◽  
Differentially Expressed ◽  
Gtpase Activating Protein ◽  
Significant Differential Expression ◽  
Primary Tumors

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding Rho GTPase-activating protein 20, ARHGAP20, when comparing primary tumors of the breast to the tissue of origin, the normal breast. ARHGAP20 mRNA was present at significantly lower quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of ARHGAP20 in primary tumors of the breast was correlated with overall survival in patients with HER2+ subtype cancer, demonstrating a relationship between primary tumor expression of a differentially expressed gene and patient survival outcomes influenced by PAM50 molecular subtype. ARHGAP20 may be of relevance to initiation, maintenance or progression of cancers of the female breast.

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