Functional importance of RASSF1A microtubule localization and polymorphisms

El-Kalla, Mohamed; Onyskiw, Christina; Baksh, Shairaz

doi:10.1038/onc.2010.316

Cited by 40 publications

(63 citation statements)

References 44 publications

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“…Recently, El-Kalla et al (2010) showed that RASSF1A Ala133Ser polymorphism also lost the ability to associate with α-and γ-tubulin and lost the ability to prevent tumor formation in a xenograft nude mouse model when compared with wild type RASSF1A. These results are consistent with my meta-analysis that RASSF1A Ala133Ser polymorphism is associated with risk of cancer.…”

Section: Discussionsupporting

confidence: 82%

“…A guanine (G)/thymine (T) common single nucleotide polymorphism (SNP) at first position of codon 133 in exon 3 of RASSF1A (dbSNP ID: rs2073498), resulting in the substitution of an alanine (Ala) residue (GCT) by serine (Ser) residue (TCT) (c.397G>T, also designated RASSF1A Ala133Ser) in the ATM phosphorylation site, has been demonstrated to affect RASSF1A function (Shivakumar et al, 2002;El-Kalla et al, 2010). To date, a few molecular epidemiological studies have investigated the association between the RASSF1A Ala133Ser polymorphism and the cancer risk including breast cancer (Schagdarsurengin et al, 2005;Gao et al, 2008;Bergqvist et al, 2010;Donninger et al, 2011), lung cancer (Kanzaki et al, 2006;Xiao et al 2012), colorectal cancer (Kanzaki et al, 2006), head and neck cancer (Kanzaki et al, 2006), esophageal cancer (Kanzaki et al, 2006;Zhou et al, 2013), renal cell carcinoma (Kawai et al, 2012), hepatocellular carcinoma (Bayram, 2012), gastric cancer (Zhou et al, 2013), prostate cancer (Meyer et al, 2013).…”

Section: Research Articlementioning

confidence: 99%

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Association between RASSF1A Ala133Ser Polymorphism and Cancer Susceptibility: A Meta-Analysis Involving 8,892 Subjects

Bayram

2014

Asian Pacific Journal of Cancer Prevention

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Background: Published studies on the association between the Ras Association Domain Family 1 isoform A (RASSF1A) Ala133Ser polymorphism and cancer susceptibility have yielded conflicting results. Thus, a metaanalysis was here performed to assess the possible association. Materials and Methods: All eligible case-control studies published up to November 2013 on the association between RASSF1A Ala133Ser polymorphism and cancer susceptibility were identified by searching PubMed, Web of Science, Science Direct and hand search. Bothfixedeffect and random-effect models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs) by using the Comprehensive Meta-Analysis software version 2.2. Results: A total of 10 studies including 4,572 cancer cases and 4,320 controls were included in the meta-analysis. Overall, significantly increased cancer risk was associated with the variant Ser133 when all studies were pooled (Ser vs Ala: OR=1.51, 95% CI=1.08-2.12, P heterogeneity ≤0.001; Ser/Ser+Ala/Ser vs Ala/Ala: OR=1.55, 95% CI=1.08-2.22, P heterogeneity ≤0.001). Moreover, in subgroup analyses by cancer types, a significant association between RASSF1A Ala133Ser polymorphism and lung cancer risk was found (Ser vs Ala: OR=2.27, 95% CI=1.29-4.02, Pheterogeneity=0.61; Ser/Ser+Ala/ Ser vs Ala/Ala: OR=2.42, 95% CI=1.33-4.42, P heterogeneity =0.75). In addition, in subgroup analyses by ethnicity, it was found that the RASSF1A Ala133Ser polymorphism was associated with overall cancer risk in Asians (Ser vs Ala: OR=1.37, 95% CI=1.06-1.77, P heterogeneity =0.06) and Caucasians (Ser/Ser+Ala/Ser vs Ala/Ala: OR=2.21, 95% CI=1.01-4.82, P heterogeneity ≤0.001). Conclusions: This meta-analysis suggests, for the first time, that RASSF1A Ala133Ser polymorphism may contribute to cancer susceptibility, especially for lung cancer. Besides, additional well-designed studies with larger sample size focusing on different ethnicities and cancer types are needed to confirm these findings.

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Section: Discussionsupporting

confidence: 82%

Section: Research Articlementioning

confidence: 99%

Association between RASSF1A Ala133Ser Polymorphism and Cancer Susceptibility: A Meta-Analysis Involving 8,892 Subjects

Bayram

2014

Asian Pacific Journal of Cancer Prevention

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“…Thus, despite harboring 60% amino acid identity (mainly after amino acid 121 of RASSF1A), RASSF1A and RASSF1C display distinctive biological properties. Several groups have demonstrated the importance of RASSF1A for microtubule stability and have mapped residues important for this function [10,14,[19][20][21]. RASSF1A interacts with microtubules though interaction with microtubule associated proteins, such as MAP1B (microtubule-associated protein 1B) and MAP1S (microtubule-associated protein 1S) [14].…”

Section: Kdamentioning

confidence: 99%

“…The C1 domain has also been demonstrated to allow for the association of RASSF1A with death receptor complexes, such as TNF-R1 and TRAIL [10]. The ATM phosphorylation site has been found to be phosphorylated in several RASSF proteins upon DNA damage/repair [11] (Reviewed in [12]).…”

Section: Introductionmentioning

confidence: 99%

RASSF tumor suppressor gene family: Biological functions and regulation

et al. 2014

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a b s t r a c tGenetic changes through allelic loss and nucleic acid or protein modifications are the main contributors to loss of function of tumor suppressor proteins. In particular, epigenetic silencing of genes by promoter hypermethylation is associated with increased tumor severity and poor survival. The RASSF (Ras association domain family) family of proteins consists of 10 members, many of which are tumor suppressor proteins that undergo loss of expression through promoter methylation in numerous types of cancers such as leukemia, melanoma, breast, prostate, neck, lung, brain, colorectal and kidney cancers. In addition to their tumor suppressor function, RASSF proteins act as scaffolding agents in microtubule stability, regulate mitotic cell division, modulate apoptosis, control cell migration and cell adhesion, and modulate NFjB activity and the duration of inflammation. The ubiquitous functions of these proteins highlight their importance in numerous physiological pathways. In this review, we will focus on the biological roles of the RASSF family members and their regulation.

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“…RASSF1A also induces prometaphase arrest through interaction with Cdc20, an activator of the anaphase-promoting complex (APC) and consequent blockade of the APC-Cdc20 interaction (13). RASSF1A also binds to and stabilizes microtubules and controls the tubulin dynamics, which is intimately related with its capacity to promote cellcycle arrest and suppress cell motility (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

RASSF1A Directly Antagonizes RhoA Activity through the Assembly of a Smurf1-Mediated Destruction Complex to Suppress Tumorigenesis

Lee

Jeong

et al. 2016

Cancer Research

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RASSF1A is a tumor suppressor implicated in many tumorigenic processes; however, the basis for its tumor suppressor functions are not fully understood. Here we show that RASSF1A is a novel antagonist of protumorigenic RhoA activity. Direct interaction between the C-terminal amino acids (256-277) of RASSF1A and active GTP-RhoA was critical for this antagonism. In addition, interaction between the N-terminal amino acids (69-82) of RASSF1A and the ubiquitin E3 ligase Smad ubiquitination regulatory factor 1 (Smurf1) disrupted GTPase activity by facilitating Smurf1-mediated ubiquitination of GTP-RhoA. We noted that the RhoA-binding domain of RASSF1A displayed high sequence homology with Rho-binding motifs in other RhoA effectors, such as Rhotekin. As predicted on this basis, RASSF1A competed with Rhotekin to bind RhoA and to block its activation. RASSF1A mutants unable to bind RhoA or Smurf1 failed to suppress RhoA-induced tumor cell proliferation, drug resistance, epithelial-mesenchymal transition, migration, invasion, and metastasis. Clinically, expression levels of RASSF1A and RhoA were inversely correlated in many types of primary and metastatic tumors and tumor cell lines. Collectively, our findings showed how RASSF1A may suppress tumorigenesis by intrinsically inhibiting the tumorpromoting activity of RhoA, thereby illuminating the potential mechanistic consequences of RASSF1A inactivation in many cancers.

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Functional importance of RASSF1A microtubule localization and polymorphisms

Cited by 40 publications

References 44 publications

Association between RASSF1A Ala133Ser Polymorphism and Cancer Susceptibility: A Meta-Analysis Involving 8,892 Subjects

Association between RASSF1A Ala133Ser Polymorphism and Cancer Susceptibility: A Meta-Analysis Involving 8,892 Subjects

RASSF tumor suppressor gene family: Biological functions and regulation

RASSF1A Directly Antagonizes RhoA Activity through the Assembly of a Smurf1-Mediated Destruction Complex to Suppress Tumorigenesis

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