Down-regulation of MTUS1 in human colon tumors

Zuern, Christina; Heimrich, Jutta; Kaufmann, Roland; Richter, Konrad Klaus; Settmacher, Utz; Wanner, Christoph; Galle, Jan; Seibold, Stefan

doi:10.3892/or_00000621

Cited by 33 publications

(36 citation statements)

References 18 publications

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“…Univariate and multivariate logistic regression analysis for disease-free survival. that MTUS1 expression is significantly downregulated in colon cancer tissues, compared with the corresponding normal tissues, at the protein and mRNA levels (20). The authors also found that knockdown of MTUS1 in HUVEC cells by siRNA transfection resulted in increased cell proliferation.…”

Section: Discussionsupporting

confidence: 53%

Reduced expression of MTUS1 mRNA is correlated with poor prognosis in bladder cancer

et al. 2012

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Abstract. Mitochondrial tumor suppressor 1 (MTUS1) is a newly identified candidate tumor suppressor gene. Previous studies have demonstrated that the expression status of MTUS1 is altered in several types of tumors. However, its clinical significance for bladder cancer patients remains undetermined. In this study, we detected the expression of MTUS1 mRNA in bladder tumors and paired normal samples obtained from 5 patients using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). A significant downregulation of MTUS1 mRNA expression was observed in the tumor tissues compared with the corresponding normal bladder tissue (P<0.001). We further tested the expression of MTUS1 mRNA in 55 bladder cancer tissues and 10 adjacent normal bladder tissues by quantitative real-time RT-PCR. Correlations between MTUS1 and clinicopathological features and prognosis were investigated by statistical analyses. The results showed that MTUS1 expression was correlated with tumor grade, stage, size and number (P<0.001, P<0.001, P= 0.034 and P= 0.029, respectively). Patients with low levels of MTUS1 mRNA expression had a poor prognosis compared with those with a high expression (P<0.001). Univariate and multivariate logistic regression prognostic analyses revealed that MTUS1 mRNA was an independent prognostic factor for disease-free survival in bladder cancer (P<0.05). In conclusion, these data suggest that MTUS1 is significant in the progression of bladder cancer and that the status of MTUS1 mRNA expression is a novel prognostic marker for predicting bladder tumor disease-free survival. IntroductionBladder cancer is a common disease, with an estimated 386,300 new cases and 150,200 mortalities occurring in 2008 worldwide (1). The disease ranks ninth in worldwide cancer incidence and is the seventh most common malignancy in men (2). In China, bladder cancer is the most common malignant neoplasm of the male urogenital system and the incidence of bladder cancer has shown an upward trend in the past two decades (3).Tumorigenesis is a multistep process during which cells acquire genetic alterations that drive the progressive transformation of normal cells into malignant cells. Genetic events which result in the progression of bladder cancer are complicated and poorly understood. Despite being a common cancer worldwide, the management of bladder cancer currently relies primarily on clinical staging and histopathological parameters. Of newly diagnosed bladder cancer cases, 70-80% present with non-muscle-invasive disease and, despite endoscopic and intravesical treatments, 50-70% recur and 10-30% progress to muscle-invasive disease (4). Thus, it is of great value to explore the mechanism of bladder cancer genesis and progression and to identify the molecular markers that predict bladder cancer recurrence and progression.Mitochondrial tumor suppressor 1 (MTUS1), also known as ATIP [angiotensin Ⅱ receptor subtypes 2 (AT2)-interacting protein], is a newly identified candidate tumor suppressor gene (5). Multiple splice transc...

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Section: Discussionsupporting

confidence: 53%

Reduced expression of MTUS1 mRNA is correlated with poor prognosis in bladder cancer

et al. 2012

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“…Other studies have shown that the MTUS1 gene encoding ATIP3 is significantly downregulated in various types of cancers including from the pancreas (32), ovary (33), head-andneck (34,35), colon (36), and bladder (37). Low MTUS1 levels were also correlated with reduced overall survival of the patients with bladder cancer (37) and oral tongue squamous cell carcinomas (35), highlighting the potential importance of ATIP3 as a new prognostic marker in a variety of solid tumors.…”

Section: Discussionmentioning

confidence: 78%

ATIP3, a Novel Prognostic Marker of Breast Cancer Patient Survival, Limits Cancer Cell Migration and Slows Metastatic Progression by Regulating Microtubule Dynamics

et al. 2013

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Metastasis, a fatal complication of breast cancer, does not fully benefit from available therapies. In this study, we investigated whether ATIP3, the major product of 8p22 MTUS1 gene, may be a novel biomarker and therapeutic target for metastatic breast tumors. We show that ATIP3 is a prognostic marker for overall survival among patients with breast cancer. Notably, among metastatic tumors, low ATIP3 levels associate with decreased survival of the patients. By using a well-defined experimental mouse model of cancer metastasis, we show that ATIP3 expression delays the time-course of metastatic progression and limits the number and size of metastases in vivo. In functional studies, ATIP3 silencing increases breast cancer cell migration, whereas ATIP3 expression significantly reduces cell motility and directionality. We report here that ATIP3 is a potent microtubule-stabilizing protein whose depletion increases microtubule dynamics. Our data support the notion that by decreasing microtubule dynamics, ATIP3 controls the ability of microtubule tips to reach the cell cortex during migration, a mechanism that may account for reduced cancer cell motility and metastasis. Of interest, we identify a functional ATIP3 domain that associates with microtubules and recapitulates the effects of ATIP3 on microtubule dynamics, cell proliferation, and migration. Our study is a major step toward the development of new personalized treatments against metastatic breast tumors that have lost ATIP3 expression. Cancer Res; 73(9); 2905-15. Ó2013 AACR.

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“…As stated above, MTUS1 is most likely a tumor suppressor gene. 74,75,85 The down-regulation of ADAMDEC1 and EPHX2 were recently associated with colon cancer metastasis, 86 and PPP2CB codes for the catalytic component of tumor suppressor protein phosphatase 2A. 87 We now hypothesize that the poor CRC prognostication of 8p loss may be explained by the fact that it harbors a number of genes with tumor suppressive properties and which play crucial roles in later stages of carcinogenesis.…”

Section: Integrated Analyses Of Snp Array Expression Array and Clinmentioning

confidence: 99%

“…73 It is not surprising then that our own analysis revealed that MAP2K4 is one of the most highly down-regulated genes within the frequently lost 17p arm. Among the genes we found to be underexpressed in CRCs because of 8p loss is MTUS1 (the down-regulation of this gene in CRCs has also been reported by another group 74 ). MTUS1 codes for a mitotic spindle-associated protein shown to be involved in the eventual reduction of mitotic rate.…”

mentioning

confidence: 98%

Gene Dysregulations Driven by Somatic Copy Number Aberrations-Biological and Clinical Implications in Colon Tumors

Bacolod

Barany

2010

The Journal of Molecular Diagnostics

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The majority of colorectal cancer (CRC) cases have chromosomal instability , in which the tumor genome is characterized by gross chromosomal aberrations such as gains in 20q , 13q , 8q , and 7 , and losses in 4, 8p , 18q , and 17p. These somatic copy number changes (gains , losses , and somatic uniparental disomies) are crucial to CRC progression as they drive genes toward cancer-promoting (oncogenic or tumor suppressive) states. Numerous studies have shown that the loss of 18q or 8p is associated with poorer clinical outcome in CRCs. Either chromosomal arm may contain a tumor suppressor gene (or genes), whose deactivation by copy loss (loss of wild-type allele , decreased expression) can be crucial to the later stages of cancer progression. Our own integrated genomic analysis (single nucleotide polymorphism array , expression array) of more than 200 CRC tumor and normal samples indicates that the overall down-regulation of genes within the 8p or 18q arm is associated with lower survival rate. Among the often down-regulated , poor prognosis-associated 8p genes is MTUS1, whose gene product (a mitotic spindleassociated protein) was recently demonstrated to have a tumor suppressive property. Within 18q is ATP5A1 , which codes for the catalytic a component of mitochondrial H ؉ -ATP synthase. Like SMAD4(also in 18q) , the decreased expression of ATP5A1 appears to be a marker of unfavorable clinical outcome in

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Down-regulation of MTUS1 in human colon tumors

Cited by 33 publications

References 18 publications

Reduced expression of MTUS1 mRNA is correlated with poor prognosis in bladder cancer

Reduced expression of MTUS1 mRNA is correlated with poor prognosis in bladder cancer

ATIP3, a Novel Prognostic Marker of Breast Cancer Patient Survival, Limits Cancer Cell Migration and Slows Metastatic Progression by Regulating Microtubule Dynamics

Gene Dysregulations Driven by Somatic Copy Number Aberrations-Biological and Clinical Implications in Colon Tumors

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