RhoA protein expression correlates positively with degree of malignancy in astrocytomas

Yan, Benedict; Chour, Han Hwan; Peh, Bee Keow; Lim, Chinghway; Salto-Tellez, Manuel

doi:10.1016/j.neulet.2006.08.032

Cited by 33 publications

(36 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results showed that the expression of RhoA is higher in grade IV as compared to grade I astrocytoma. This supports the notion that RhoA expression increases as the degree of astrocytoma tumor malignancy increases in accordance with the results of Yan et al (2006).…”

Section: Discussionsupporting

confidence: 91%

“…Two reports have addressed this matter, the first one reported a significantly increased expression of RhoA in high-grade astrocytomas (WHO grades III and IV) as compared to low-grade astrocytomas (WHO grades I and II) (Yan, et al, 2006); however, the second study showed that RhoA expression is significantly decreased in astrocytic tumors as compared to normal brain, and that this expression decreases as the degree of tumor malignancy increases (Forget, et al, 2002). Hence, in order to further investigate this, we measured the level of RhoA expression in astrocytoma tumors by immunohistochemistry.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the Rac1 expression level was reduced in astrocytic tumors of grades III and IV (Forget, et al, 2002). However, another study that was based on the analysis of clinical materials demonstrated that the expression of RhoA is increased in high-grade astrocytomas (Yan, Chour, Peh, Lim, & Salto-Tellez, 2006). Rac2 was also found to be underexpressed in 57.7% of brain tumors (Hwang, et al, 2005).…”

mentioning

confidence: 99%

See 2 more Smart Citations

The regulation of Rhoa in focal adhesions by starD13 is essential for astrocytoma cell motility. (c2011)

Khalil¹

View full text Add to dashboard Cite

Malignant astrocytomas are associated with poor prognosis and high morbidity and mortality rates despite intensive treatment. These tumors rarely metastasize into distant regions of the body; however, they are highly invasive into adjacent and distant regions of the normal brain, which renders them surgically and medically unmanageable and accounts for their fatal outcome.Invasion is a multistep process, which ultimately requires the cell to actively migrate through the ECM. Proper cell adhesion dynamics, involving the assembly and the disassembly of adhesion, is essential for the completion of the motility cycle. Rho-GTPases, mainly RhoA, Rac, and Cdc42, play a major role in the regulation of the processes that ultimately lead to cell migration. StarD13 is a RhoGAP that inhibits the function of RhoA and Cdc42.We first aimed at determining the role of RhoA in the progression of astrocytic tumors, a topic that is still controversial in the literature. Our results showed that RhoA plays a positive role in this aspect.Our current study also investigates the roles of RhoA, Rac1, and StarD13 in cell adhesion and cell migration. Our results showed that RhoA, Rac1, and StarD13 are essential for astrocytoma cell migration. Rac1 plays a role in the formation of focal complexes, which ultimately mature into focal adhesions under the action of RhoA. StarD13 plays a role in the inhibition of RhoA in focal complexes, a process that seems indispensible for astrocytoma cell migration. The incidence rate of primary malignant brain and central nervous system tumors is 6.4 cases per 100,000 person-years (Horner, et al., 2009). This rate of occurrence is higher in males than it is in females (7.6 compared to 5.4 per 100,000 person-years respectively).The lifetime risk of developing a primary malignant brain or a central nervous system tumor is 0.67% in males and 0.54% in females (Horner, et al., 2009). The chance of dying from a brain or a central nervous system tumor is 0.48% in males compared to 0.38% in females (Horner, et al., 2009). ClassificationThe (CBTRUS, 2011;Louis, et al., 2007). Gliomas can either be low-grade or high-grade (malignant). Malignant gliomas are pathologically, histologically, and genetically heterogeneous tumors and they are known to be invasive (DeAngelis, 2001). AstrocytomasAstrocytomas are gliomas that arise from astrocytes (Louis, et al., 2007). Based on the classification of the World Health Organization (WHO), astrocytomas are assigned into one of four prognostic grades: grade I (pilocytic astrocytoma), grade II (diffuse astrocytoma), grade III (anaplastic astrocytoma), and grade IV (glioblastoma), with grades III and IV considered malignant (Louis, et al., 2007). Malignant astrocytomas are usually associated with a poor prognosis and high morbidity and mortality rates despite intensive treatment.The median survival time is 12 to 14 months for patients with glioblastoma and 2 to 5 years for patients with anaplastic astrocytoma (Wen & Kesari, 2008). For unclear reasons, malignant astrocyt...

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

The regulation of Rhoa in focal adhesions by starD13 is essential for astrocytoma cell motility. (c2011)

Khalil¹

View full text Add to dashboard Cite

show abstract

“…Another Rho GTPases, RhoA plays a negatively regulatory role in GBM progression [19][20][21][22]. Decreased RHOA activity related to increase of glioma cell migration [19][20][21][22].…”

Section: Discussionmentioning

confidence: 99%

“…Decreased RHOA activity related to increase of glioma cell migration [19][20][21][22]. Functional studies suggested that the inhibition of RhoA's effector ROCK led to the invasion of glioma cells and the activation of Rac1 [23].…”

Section: Discussionmentioning

confidence: 99%

Differential Proteomics Analysis of Oligodendrogliomas and Astrocytomas Using iTRAQ Quantification

Shi

Wang

et al. 2017

J Proteomics Bioinform

View full text Add to dashboard Cite

Novel CTRP8‐RXFP1‐JAK3‐STAT3 axis promotes Cdc42‐dependent actin remodeling for enhanced filopodia formation and motility in human glioblastoma cells

et al. 2021

View full text Add to dashboard Cite

C1q tumor necrosis factor-related peptide 8 (CTRP8) is the least studied member of the C1Q-TNF-related peptide family. We identified CTRP8 as a ligand of the G protein-coupled receptor relaxin family peptide receptor 1 (RXFP1) in glioblastoma multiforme (GBM). The CTRP8-RXFP1 ligand-receptor system protects human GBM cells against the DNA-alkylating damage-inducing temozolomide (TMZ), the drug of choice for the treatment of patients with GBM. The DNA protective role of CTRP8 was dependent on a functional RXFP1-STAT3 signaling cascade and targeted the monofunctional glycosylase N-methylpurine DNA glycosylase (MPG) for more efficient base excision repair of TMZ-induced DNA-damaged sites. CTRP8 also improved the survival of GBM cells by upregulating anti-apoptotic BCl-2 and BCL-XL. Here, we have identified Janus-activated kinase 3 (JAK3) as a novel member of a novel CTRP8-RXFP1-JAK3-STAT3 signaling cascade that caused an increase in cellular protein content and activity of the small Rho GTPase Cdc42. This is associated with significant F-actin remodeling and increased GBM motility. Cdc42 was critically important for the upregulation of the actin nucleation complex N-Wiskott-Aldrich syndrome protein/Arp3/4 and actin elongation factor profilin-1. The activation of the RXFP1-JAK3-STAT3-Cdc42 axis by both RXFP1 agonists, CTRP8 and relaxin-2, caused extensive filopodia formation. This coincided with enhanced activity of ezrin, a key factor in tethering F-actin to the plasma membrane, and inhibition of the actin filament severing activity of cofilin. The F-actin remodeling and pro-migratory activities promoted by the novel RXFP1-JAK3-STAT3-Cdc42 axis were blocked by JAK3 inhibitor tofacitinib and STAT3 inhibitor STAT3 inhibitor VI. This provides a new rationale for the design of JAK3 and STAT3 inhibitors with better brain permeability for clinical treatment of the pervasive brain invasiveness of GBM.

show abstract

RhoA protein expression correlates positively with degree of malignancy in astrocytomas

Cited by 33 publications

References 14 publications

The regulation of Rhoa in focal adhesions by starD13 is essential for astrocytoma cell motility. (c2011)

The regulation of Rhoa in focal adhesions by starD13 is essential for astrocytoma cell motility. (c2011)

Differential Proteomics Analysis of Oligodendrogliomas and Astrocytomas Using iTRAQ Quantification

Novel CTRP8‐RXFP1‐JAK3‐STAT3 axis promotes Cdc42‐dependent actin remodeling for enhanced filopodia formation and motility in human glioblastoma cells

Contact Info

Product

Resources

About