Harrison SC, etal., Eur Heart J. 2012 Apr;33(7):881-8. doi: 10.1093/eurheartj/ehr075. Epub 2011 Mar 28.
AIMS: A sequence variant, rs7025486[A], in DAB2IP on chromosome 9q33 has recently been associated with coronary heart disease (CHD). We sought to replicate this finding and to investigate associations with a panel of inflammatory and haemostatic bioma
rkers. We also sought to examine whether this variant, in combination with a chromosome 9p21 CHD variant (rs10757278) and the Framingham risk score (FRS), could improve the prediction of events compared with the FRS alone. METHODS AND RESULTS: rs7025486 was genotyped in 1386 CHD cases and 3532 controls and was associated with CHD [odds ratio (OR) of 1.16, 95% confidence interval (CI) 1.05-1.29, P= 0.003]. Meta-analysis, using data from the original report and from genome-wide association studies in both the Wellcome Trust Case Control Consortium and the Cardiovascular Health Study, comprising 9968 cases and 20 048 controls, confirmed the association (OR of 1.10, 95% CI 1.06-1.14, P= 3.2 × 10(-6)). There was no association with a panel of CHD biomarkers, including any lipid, inflammation, or coagulation trait, nor with telomere length. Addition to the FRS of this variant plus rs10757278 on chromosome 9p21 improved the area under the receiver-operating characteristic curve (A(ROC)) from 0.61 to 0.64 (P= 0.03) as well as improving the reclassification (net reclassification index = 11.1%, P= 0.007). CONCLUSION: This study replicates a previous association of a variant in DAB2IP with CHD. Addition of multiple variants improves the performance of predictive models based upon classical cardiovascular risk factors.
Shan N, etal., J Matern Fetal Neonatal Med. 2016;29(3):393-9. doi: 10.3109/14767058.2014.1001974. Epub 2015 Jan 21.
OBJECTIVE: DAB2IP is a growth inhibitor present in many types of cancer cells and is associated with epigenetic regulations controlling tumor development. The primary objective of this study is to determine whether DAB2IP pa
rticipates in the invasion and migration of trophoblasts during placental development. METHODS: The expressions of DAB2IP in human placentas (10 villi, 18 term placentas and 20 pre-eclampsia placentas) were determined by immunohistochemistry, Western blotting and quantitative RT-PCR. HTR8/SVneo cells were treated with hypoxia-reoxygenation (H/R) to test how DAB2IP expression would affect the invasion and migration of trophoblasts. JEG-3 andHTR8/SVneo cells were treated with 5-aza-2-deoxycytidine (5-aza-dC) to study the role of DAB2IP promoter methylation in trophoblasts. RESULTS: DAB2IP was strongly expressed in human villi and extravillous trophoblasts as well as in HTR8/SVneo cells, but not in pre-eclampsia placentas. DAB2IP expression increased after H/R treatment, but the invasive and migratory abilities of trophoblasts were reduced. DAB2IP expression in JEG-3 cells also increased after treatment with 5-aza-dC. CONCLUSIONS: These findings strongly suggest that DAB2IP is an important negative regulator at the maternal-fetal interface during early pregnancy. Excessive oxidative stress can increase DAB2IP expression in trophoblasts. The mechanism of DNA methylation may involve in its function during the development of pathologic pregnancy.
Xiao Y, etal., Eur Rev Med Pharmacol Sci. 2019 Apr;23(8):3326-3334. doi: 10.26355/eurrev_201904_17695.
OBJECTIVE: Colorectal cancer (CRC) remains one of the most frequent lethal malignant tumors worldwide. The correlation between miR-889 expression and CRC progression has not been well identified in the recent literature. Here, we aim to detect the role and mechanism of miR-889 in CRC.
PATIENTS AND METHODS: First, miRNA RT-PCR (Real Time-Polymerase Chain Reaction) was performed to determine miR-889 expression in CRC tissues and cells. The proliferative capacity of cells transfected with miR-889 mimics, miR-889 inhibitor or NC was measured by CCK-8 (cell counting kit-8), colony formation and EdU (5-Ethynyl-2'-deoxyuridine) assays. The online bioinformatics sites were chosen to predict possible downstream regulatory genes of miR-899. The dual-luciferase report assay was conducted to verify the relation between DAB2IP (DAB2 interacting protein) and miR-899. The expression changes of DAB2IP were assessed by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. RESULTS: MiR-889 was upregulated in CRC tissues and CRC cells, and upregulated miR-889 was confirmed to promote cell growth in vitro. Dual-luciferase reporter, qRT-PCR, and Western blot assays suggested that DAB2IP might be regulated by miR-889. The effects of miR-889 on proliferation could be abolished by DAB2IP through confirmatory experiments. By directly targeting DAB2IP, miR-889 served as a vital part in accelerating CRC cell proliferation. CONCLUSIONS: Our current study substantiated that miR-889 might participate in controlling CRC proliferation by regulating DAB2IP, which provides potential and prospective therapeutic target for CRC.
A faster expansion rate of abdominal aortic aneurysm (AAA) increases the risk of rupture. Women are at higher risk of rupture than men, but the mechanisms underlying this increased risk are unknown. We investigated whether genetic variants that influence susceptibility for AAA (CDKN2A-2B, SORT1, ... (more)
an style='font-weight:700;'>DAB2IP, LRP1 and LDLR) are associated with AAA expansion and whether these associations differ by sex in 650 patients with AAA (mean age 70±8 years, 17% women) enrolled in the Mayo Clinic Vascular Disease Biorepository. Women had a mean aneurysm expansion 0.41 mm/year greater than men after adjustment for baseline AAA size. In addition to baseline size, mean arterial pressure (MAP), non-diabetic status, SORT1-rs599839[G] and DAB2IP-rs7025486[A] were associated with greater aneurysm expansion (all p<0.05). The associations of MAP and rs599839[G] were similar in both sexes, while the associations of baseline size, pulse pressure (PP) and rs7025486[A] were stronger in women than men (all p-sex interaction <=0.02). A three-way interaction of PP*sex* rs7025486[A] was noted in a full-factorial analysis (p=0.007) independent of baseline size and MAP. In the high PP group (>=median), women had a mean growth rate 0.68 mm/year greater per [A] of rs7025486 than men (p-sex interaction =0.003), whereas there was no difference in the low PP group (p-sex interaction =0.8). We demonstrate that variants DAB2IP-rs7025486[A] and SORT1-rs599839[G] are associated with AAA expansion. The association of rs7025486[A] is stronger in women than men and amplified by high PP, contributing to sex differences in aneurysm expansion.
Legaki E, etal., In Vivo. 2019 May-Jun;33(3):737-742. doi: 10.21873/invivo.11533.
BACKGROUND/AIM: Nine genetic loci have been associated with abdominal aortic aneurysm (AAA) susceptibility, including DAB2IP. This gene is playing a role in apoptosis, cell proliferation and epithelial-to-mesenchymal transition in cancers. This study
aimed to elucidate the differential expression levels of DAB2IP in AAA tissues and investigate whether mir-363-3p and EZH2 can be considered as potential mediators of its expression. MATERIALS AND METHODS: 18 AAA samples and 15 non-aneurysmatic controls were collected. Relative mRNA expression levels of DAB2IP, EZH2 and mir-363-3p were measured using qPCR. RESULTS: DAB2IP was significant up-regulated (~2.29 fold) in AAA tissues, while EZH2 and mir-363-3p were down-regulated (3.28 and 3.62-fold, respectively). A limited negative correlation was found between the DAB2IP and EZH2 expression and between DAB2IP and the mir-363-3p. CONCLUSION: An increased expression of DAB2IP in AAA tissues was shown. We suggest 2 potential mediators of DAB2IP expression in abdominal aortic aneurysm, EZH2 and mir-363-3p.
Harrell Stewart DR, etal., Cancers (Basel). 2020 Dec 17;12(12). pii: cancers12123807. doi: 10.3390/cancers12123807.
Lung cancer is the leading cause of cancer-related death worldwide. Lung cancer is commonly driven by mutations in the RAS oncogenes, the most frequently activated oncogene family in human disease. RAS-induced tumorigenesis is inhibited by the tumor suppressor RASSF1A, which induces apoptosis in res
ponse to hyperactivation of RAS. RASSF1A expression is suppressed in cancer at high rates, primarily owing to promoter hypermethylation. Recent reports have shown that loss of RASSF1A expression uncouples RAS from apoptotic signaling in vivo, thereby enhancing tumor aggressiveness. Moreover, a concomitant upregulation of RAS mitogenic signaling upon RASSF1A loss has been observed, suggesting RASSF1A may directly regulate RAS activation. Here, we present the first mechanistic evidence for control of RAS activation by RASSF1A. We present a novel interaction between RASSF1A and the Ras GTPase Activating Protein (RasGAP) DAB2IP, an important negative regulator of RAS. Using shRNA-mediated knockdown and stable overexpression approaches, we demonstrate that RASSF1A upregulates DAB2IP protein levels in NSCLC cells. Suppression of RASSF1A and subsequent downregulation of DAB2IP enhances GTP loading onto RAS, thus increasing RAS mitogenic signaling in both mutant- and wildtype-RAS cells. Moreover, co-suppression of RASSF1A and DAB2IP significantly enhances in vitro and in vivo growth of wildtype-RAS cells. Tumors expressing wildtype RAS, therefore, may still suffer from hyperactive RAS signaling when RASSF1A is downregulated. This may render them susceptible to the targeted RAS inhibitors currently in development.
Yang L, etal., PLoS One. 2011;6(10):e26944. doi: 10.1371/journal.pone.0026944. Epub 2011 Oct 26.
DOC-2/DAB2 interactive protein (DAB2IP) is a novel identified tumor suppressor gene that inhibits cell growth and facilitates cell apoptosis. One genetic variant in DAB2IP gene was reported to be associated with an increased
risk of aggressive prostate cancer recently. Since DAB2IP involves in the development of lung cancer and low expression of DAB2IP are observed in lung cancer, we hypothesized that the variations in DAB2IP gene can increase the genetic susceptibility to lung cancer. In a case-control study of 1056 lung cancer cases and 1056 sex and age frequency-matched cancer-free controls, we investigated the association between two common polymorphisms in DAB2IP gene (-1420T>G, rs7042542; 97906C>A, rs1571801) and the risk of lung cancer. We found that compared with the 97906CC genotypes, carriers of variant genotypes (97906AC+AA) had a significant increased risk of lung cancer (adjusted odds ratio [OR] = 1.33, 95%CI = 1.04-1.70, P = 0.023) and the number of variant (risk) allele worked in a dose-response manner (P(trend) = 0.0158). Further stratification analysis showed that the risk association was more pronounced in subjects aged less than 60 years old, males, non-smokers, non-drinkers, overweight groups and in those with family cancer history in first or second-degree relatives, and the 97906A interacted with overweight on lung cancer risk. We further found the number of risk alleles (97906A allele) were negatively correlated with early diagnosis age of lung cancer in male patients (P = 0.003). However, no significant association was observed on the -1420T>G polymorphism. Our data suggested that the 97906A variant genotypes are associated with the increased risk and early onset of lung cancer, particularly in males.
Min J, etal., Sci Rep. 2015 Nov 13;5:16578. doi: 10.1038/srep16578.
Metastasis is a critical factor for the high mortality of colorectal cancer (CRC), but its mechanism is not completely understood. Epithelial-mesenchymal transition (EMT) is thought to play a key role in metastasis and also increases the cancer stem cell (CSC) feature that facilitates metastatic col
onization. In this study, we investigated the biological roles of DAB2IP regulating EMT and stem cell-like features in human CRC. We demonstrate that DAB2IP suppresses NF-kappaB-mediated EMT and CSC features in CRC cells. In DAB2IP knockout mice, we discovered the hyperplasia in colonic epithelium which aberrantly represents the mesenchymal feature and NF-kappaB pathway activation. In clinic CRC tissue, we also reveal that reduced DAB2IP can enrich the CD133(+) subpopulation. DAB2IP expression was inversely correlated with tumor differentiation and metastasis, and patients with lower DAB2IP expression had shorter overall survival time. Taken together, our study demonstrates that DAB2IP inhibits NF-kappaB-inducing EMT and CSC to suppress the CRC progression, and also suggests that DAB2IP is a beneficial prediction factor for CRC patient prognosis.
Zhou J, etal., Cell Death Dis. 2015 Oct 29;6:e1955. doi: 10.1038/cddis.2015.289.
Loss of DAB2IP, a novel tumor suppressor gene, is associated with the high risk of aggressive prostate cancer (PCa). Previously, we reported that DAB2IP modulated androgen receptor activation in the development of castration
-resistant PCa; however, its direct action on the failure of androgen deprivation therapy (ADT) remains largely unknown. In this study, we showed that DAB2IP knockdown could significantly enhance in vitro growth and colony formation of PCa cells following ADT as well as tumorigenicity in pre-castrated nude mice. In addition, DAB2IP loss stabilized mitochondrial transmembrane potential, prevented release of cytochrome c, Omi/HtrA2 and Smac from the mitochondria to the cytoplasm and inhibited intrinsic apoptosis induced by ADT. Mechanistically, DAB2IP could interact with the signal transducer and activator of transcription 3 (STAT3) via its unique PR domain and suppress STAT3 phosphorylation and transactivation, leading to the inhibition of survivin expression in PCa cells. Moreover, the luminal epithelia in DAB2IP(-/-) mice with more activated STAT3 and survivin expression were resistant to castration-induced apoptosis. Consistently, DAB2IP expression inversely correlated with STAT3 phosphorylation and survivin expression in PCa patients. Together, our data indicate that DAB2IP loss reprograms intracellular signal transduction and anti-apoptotic gene expression, which potentiates PCa cell survival from ADT-induced cell death.
There is a high frequency of tumor recurrence in non-muscle invasive bladder cancer (NMIBC) after transurethral resection and postoperative intravesical chemotherapy, however, the molecular mechanisms leading to the chemoresistance and tumor re-growth remain largely unknown. In this study, we observ
ed a significant decrease of DAB2IP expression in high-grade and recurrent NMIBC specimens, which was negatively correlated with Twist1 expression and predicted a lower recurrence-free survival of patients. Mechanistically, DAB2IP could inhibit the phosphorylation and transactivation of STAT3, and then subsequently suppress the expression of Twist1 and its target gene P-glycoprotein, both of which were crucial for the pirarubicin chemoresistance and tumor re-growth of bladder cancer cells. Overall, this study reveals a new promising biomarker modulating the chemoresistance and tumor recurrence of NMIBC after bladder preservation surgery.
DOC-2/DAB2 interacting protein (DAB2IP) is a RasGAP protein that shows a suppressive effect on cancer progression. Our previous study showed the involvement of transcription regulation of DAB2IP in metastasis of colorectal c
ancer (CRC). However, the molecular mechanisms of DAB2IP in regulating the progression of CRC need to be further explored. Here, we identified heterogeneous nuclear ribonucleoprotein K (hnRNPK) and matrix metalloproteinase 2 (MMP2) as vital downstream targets of DAB2IP in CRC cells by two-dimensional fluorescence difference gel electrophoresis and cDNA microassay, respectively. Mechanistically, down-regulation of DAB2IP increased the level of hnRNPK through MAPK/ERK signaling pathway. Subsequently, translocation of hnRNPK into nucleus enhanced the transcription activity of MMP2, and therefore promoted invasion and metastasis of CRC. Down-regulation of DAB2IP correlated negatively with hnRNPK and MMP2 expressions in CRC tissues. In conclusion, our study elucidates a novel mechanism of the DAB2IP/hnRNPK/MMP2 axis in the regulation of CRC invasion and metastasis, which may be a potential therapeutic target.
Bhanushali AA, etal., Indian Heart J. 2018 Dec;70 Suppl 3(Suppl 3):S480-S482. doi: 10.1016/j.ihj.2018.06.016. Epub 2018 Jun 19.
Genome wide association study has identified rs7025486 G>A polymorphism within DAB2IP (Disabled homolog 2-interacting protein) gene with increased risk of coronary heart disease (CAD). In this study we have determined the frequency and association of rs7025486 w
ith CAD in Indians. The study was performed on 214 patients with CAD and 125 controls. The 'AA' genotype was associated with an increased risk in the CAD age group <50 yrs as compared to CAD age group>50 yrs (OR 3.149; P 0.034) and controls >50 yrs (OR 3.430; P 0.080). The risk allele (A) was significantly associated with premature CAD.
We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to assoc
iate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 x 10(-10). In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 x 10(-5)), peripheral arterial disease (OR = 1.14, P = 3.9 x 10(-5)) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases-that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival.
Yeh CR, etal., Oncotarget. 2015 Dec 29;6(42):44346-59. doi: 10.18632/oncotarget.5884.
Previous studies indicated the T cells, one of the most common types of immune cells existing in the microenvironment of renal cell carcinoma (RCC), may influence the progression of RCC. The potential linkage of T cells and the estrogen receptor beta (ERbeta), a key player to impact RCC progression,
however, remains unclear. Our results demonstrate that RCC cells can recruit more T cells than non-malignant kidney cells. Using an in vitro matrigel invasion system, we found infiltrating T cells could promote RCC cells invasion via increasing ERbeta expression and transcriptional activity. Mechanism dissection suggested that co-culturing T cells with RCC cells released more T cell attraction factors, including IFN-gamma, CCL3 and CCL5, suggesting a positive regulatory feed-back mechanism. Meanwhile, infiltrating T cells may also promote RCC cell invasion via increased ERbeta and decreased DAB2IP expressions, and knocking down DAB2IP can then reverse the T cells-promoted RCC cell invasion. Together, our results suggest that infiltrating T cells may promote RCC cell invasion via increasing the RCC cell ERbeta expression to inhibit the tumor suppressor DAB2IP signals. Further mechanism dissection showed that co-culturing T cells with RCC cells could produce more IGF-1 and FGF-7, which may enhance the ERbeta transcriptional activity. The newly identified relationship between infiltrating T cells/ERbeta/DAB2IP signals may provide a novel therapeutic target in the development of agents against RCC.
BACKGROUND AND AIM: DOC-2/DAB2 interactive protein gene (DAB2IP) is a novel member of the Ras GTPase-activating protein family and plays a tumor suppressive role in cancer progression, but its function in hepatocellular carcinoma (HCC) remains unclear
. This aims of this study were to analyze the clinicopathological features of DAB2IP expression in HCC, and to determine the effect of DAB2IP on HCC cell behaviors in vitro. METHODS: The expression of DAB2IP was detected in hepatocyte cell line and HCC cell lines by real-time reverse transcription-polymerase chain reaction and western blot. DAB2IP expression was then examined in 120 cases of clinical paraffin-embedded HCC tissue by immunohistochemistry (IHC). 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) method and in vitro invasive assay were finally performed to evaluate the effect of DAB2IP depletion on cell proliferation or invasion of HCC cells. RESULTS: DAB2IP expression was lower in HCC cell lines or tissues than in hepatocyte cell lines, adjacent cirrhotic livers or normal livers (P < 0.05). Its expression was positively correlated with tumor size (P = 0.01). Patients with lower DAB2IP expression had shorter overall survival time (P = 0.013). DAB2IP suppresses proliferation and invasion of HCC cells in vitro. CONCLUSION: DAB2IP is a valuable marker for progression of HCC patients. Downregulation of DAB2IP is associated with poor prognosis in HCC patients. DAB2IP silence alone is sufficient to promote HCC cell proliferation and invasion in vitro.
Li X, etal., Int J Biochem Cell Biol. 2019 Jun;111:27-36. doi: 10.1016/j.biocel.2019.04.002. Epub 2019 Apr 8.
miR-182 was revealed to be upregulated in colorectal cancer (CRC) and contributed to CRC development. However, the detailed molecular mechanism of miR-182 in the progression of CRC remains largely elusive. Herein, miR-182 was upregulated in CRC serum samples, CRC tissues and cells. miR-182 expressio
n was evidently reduced in postoperative serum samples, compared with preoperative serum samples, whereas miR-182 expression was re-elevated in serum samples from CRC patients who developed postoperative recurrence. Exogenous miR-182 promoted the proliferation, colony formation, increased ki67 level and facilitated the invasion capability of CRC cells by enhancing the expressions of MMP-2 and MMP-9, while inhibition of miR-182 showed the opposite effects. Additionally, miR-182 was demonstrated to target DAB2IP and suppress its expression in CRC cells. Downregulation of miR-182 inhibited CRC tumor growth in vivo by upregulating DAB2IP. Moreover, restoration of DAB2IP attenuated miR-182-mediated activation of the PI3K/Akt/mTOR and Wnt/β-catenin pathways in CRC cells. Taken together, our findings showed that miR-182 exerted its oncogenic role in CRC by targeting DAB2IP, which may be involved in activating the PI3K/Akt/mTOR and Wnt/β-catenin pathways, shedding a novel light on the molecular mechanism of CRC tumorigenesis.
Ni QF, etal., Cell Prolif. 2020 Jan;53(1):e12630. doi: 10.1111/cpr.12630. Epub 2019 Nov 12.
OBJECTIVES: miR-92b has been reported to play critical roles in several carcinomas; however, our understanding of the mechanisms by which miR-92b stimulates gastric cancer (GC) is incomplete. The aim of this study was to investigate the clinical significance and functional relevance of mi
R-92b in GC. MATERIALS AND METHODS: Expression of miR-92b in GC and peritumoural tissues was determined using qRT-PCR, in situ hybridization and bioinformatics. CCK-8, colony formation and fluorescence-activated cell sorting assays were utilized to explore the effect of miR-92b on GC cells. A luciferase reporter assay and Western blotting were employed to verify miR-92b targeting of DAB2IP. Furthermore, Western blotting was used to evaluate the levels of DAB2IP and PI3K/Akt signalling pathway-related proteins. RESULTS: In this study, we found that miR-92b was upregulated in GC tissues compared with peritumoural tissues. Overexpression of miR-92b promoted cell proliferation, colony formation, and G0 /G1 transition and decreased apoptosis. Our results indicated that miR-92b repressed the expression of DAB2IP and that loss of DAB2IP activated the PI3K/AKT signalling pathway. Overexpression of DAB2IP rescued the effects of miR-92b in GC cells. Finally, our results demonstrated a significant correlation between miR-92b expression and DAB2IP expression in GC tissues. CONCLUSIONS: Our results suggest that miR-92b promotes GC cell proliferation by activating the DAB2IP-mediated PI3K/AKT signalling pathway. The miR-92b/DAB2IP/PI3K/AKT signalling axis may be a potential therapeutic target to prevent GC progression.
Jacobs C, etal., Cancer Med. 2015 Dec;4(12):1844-52. doi: 10.1002/cam4.554. Epub 2015 Oct 16.
Decreased expression of tumor suppressor DAB2IP is linked to aggressive cancer and radiation resistance in several malignancies, but clinical survival data is largely unknown. We hypothesized that pretreatment DAB2IP reducti
on would predict worse prostate cancer-specific survival (PCSS). Immunohistochemistry of pretreatment biopsies was scored by an expert genitourinary pathologist. Other endpoints analyzed include freedom from biochemical failure (FFBF), castration resistance-free survival (CRFS), and distant metastasis-free survival (DMFS). Seventy-nine patients with NCCN-defined high-risk prostate cancer treated with radiotherapy from 2005 to 2012 at our institution were evaluated. Twenty-eight percent (22/79) of pretreatment biopsies revealed DAB2IP-reduction. The median follow up times were 4.8 years and 5.3 years for patients in the DAB2IP-reduced group and DAB2IP-retained group, respectively. Patients with reduced DAB2IP demonstrated worse outcome compared to patients retaining DAB2IP, including FFBF (4-year: 34 vs. 92%; P < 0.0001), CRFS (4-year: 58 vs. 96%; P = 0.0039), DMFS (4-year: 58 vs. 100%; P = 0.0006), and PCSS (5-year: 83 vs. 100%; P = 0.0102). Univariate analysis showed T stage, N stage, and Gleason score were statistically significant variables. Pretreatment tumor DAB2IP status remained significant in multivariable analyses. This study suggests that about one-fourth of men with high-risk prostate cancer have decreased tumor expression of DAB2IP. This subpopulation with reduced DAB2IP has a suboptimal response and worse malignancy-specific survival following radiation therapy and androgen deprivation. DAB2IP loss may be a genetic explanation for the observed differences in aggressive tumor characteristics and radiation resistance. Further study into improving treatment response and survival in this subpopulation is warranted.
Wang J, etal., Oncotarget. 2015 Sep 29;6(29):27427-39. doi: 10.18632/oncotarget.4861.
DAB2IP has been identified as a tumor suppressor in several cancers but its oncogenic role and transcriptionally regulatory mechanisms in the progression of colorectal carcinoma (CRC) remain unknown. In this study, DAB2IP w
as down-regulated in CRC tissues and a valuable prognostic marker for survival of CRC patients, especially in the late stage. Moreover, DAB2IP was sufficient to suppress proliferation, epithelial-mesenchymal transition (EMT), invasion and metastasis in CRC. Mechanically, the linear complex of EZH2/HDAC1/Snail contributed to DAB2IP silencing in CRC cells. The study further proved that the positive feedback loop between Snail and DAB2IP existed in CRC cells and DAB2IP was required for Snail-induced aggressive cell behaviors. Finally, DAB2IP correlated negatively with Snail and EZH2 expressions in CRC tissues. Our findings reveal the suppressive role and a novel regulatory mechanism of DAB2IP expression in the progression of CRC. DAB2IP may be a potential, novel therapeutic and prognostic target for clinical CRC patients.
