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

Xiao, Jun; Chen, Junxing; Zhu, Yumeng; Zhou, Leidang; Shu, Qi-An; Chen, Lingwu

doi:10.3892/ol.2012.673

Cited by 24 publications

(30 citation statements)

References 22 publications

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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: 75%

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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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Section: Discussionmentioning

confidence: 75%

“…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: 93%

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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“…Xiao et al (11) found that MTUS1 expression was correlated with tumor grade, stage, size and number in bladder cancer, and patients with low levels of MTUS1 mRNA expression had a poor prognosis compared with those exhibiting high MTUS1 expression. Our previous study also suggested that downregulation of MTUS1/ATIP was a frequent event in TSCC and premalignant lesions, e.g., leukoplakia.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II type 2 receptor-interacting protein 3a suppresses proliferation, migration and invasion in tongue squamous cell carcinoma via the extracellular signal-regulated kinase-Snai2 pathway

Zhao

et al. 2015

Oncology Letters

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Abstract.Our previous studies demonstrated that the downregulation of microtubule-associated tumor suppressor 1/angiotensin II type 2 receptor-interacting protein (MTUS1/ATIP) is associated with poor differentiation and prognosis in tongue squamous cell carcinoma (TSCC), and that ATIP1 exerts an antiproliferative effect on TSCC. The aim of the present study was to further investigate the anticancer effect of MTUS1/ATIP3a in TSCC. It was observed that UM1 cells (a TSCC cell line with high migration and invasion ability) exhibited lower expression of ATIP3a compared with UM2 cells (a TSCC cell line with lower migration and invasion ability). Restoration of ATIP3a expression in UM1 cells exerted antiproliferative effects and inhibited migration and invasion, whereas knockdown of ATIP3a promoted proliferation, migration and invasion in UM2 cells. Restoration of ATIP3a expression inhibited the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and the expression of Snai2 and vimentin in UM1 cells, whereas knockdown of ATIP3a promoted the phosphorylation of ERK1/2 and the expression of Snai2 and vimentin in UM2 cells. Therefore, MTUS1/ATIP3a was found to suppress the proliferation, migration and invasion of TSCC cells via the ERK1/2-Snai2 pathway.

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“…In the meantime another study group also found an association between MTUS1 expression and bladder cancer [30]. …”

Section: Resultsmentioning

confidence: 99%

Loss of MTUS1/ATIP expression is associated with adverse outcome in advanced bladder carcinomas: data from a retrospective study

et al. 2014

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BackgroundSeventy percent of all bladder tumours tend to recur and need intensive surveillance, and a subset of tumours progress to muscle-invasive and metastatic disease. However, it is still difficult to find the adequate treatment for every individual patient as it is a very heterogeneous disease and reliable biomarkers are still missing. In our study we searched for new target genes in the critical chromosomal region 8p and investigated the potential tumour suppressor gene candidate MTUS1/ATIP in bladder cancer.MethodsMTUS1 was identified to be the most promising deleted target gene at 8p in aCGH analysis with 19 papillary bladder tumours. A correlation with bladder cancer was further validated using immunohistochemistry of 85 papillary and 236 advanced bladder tumours and in functional experiments. Kaplan-Meier analysis and multivariate Cox-regression addressed overall survival (OS) and disease-specific survival (DSS) as a function of MTUS1/ATIP expression. Bivariate correlations investigated associations between MTUS1/ATIP expression, patient characteristics and histopathology. MTUS1 expression was analysed in cell lines and overexpressed in RT112, where impact on viability, proliferation and migration was measured.ResultsMTUS1 protein expression was lost in almost 50% of all papillary and advanced bladder cancers. Survival, however, was only influenced in advanced carcinomas, where loss of MTUS1 was associated with adverse OS and DSS. In this cohort, there was also a significant correlation of MTUS1 expression and histological subtype: positive expression was detected in all micropapillary tumours and aberrant nuclear staining was detected in a subset of plasmocytoid urothelial carcinomas. MTUS1 was expressed in all investigated bladder cell lines and overexpression in RT112 led to significantly decreased viability.ConclusionsMTUS1 is a tumour suppressor gene in cultured bladder cancer cells and in advanced bladder tumours. It might represent one new target gene at chromosome 8p and can be used as an independent prognostic factor for advanced bladder cancer patients. The limitation of the study is the retrospective data analysis. Thus, findings should be validated with a prospective advanced bladder tumour cohort.

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

Cited by 24 publications

References 22 publications

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

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

Angiotensin II type 2 receptor-interacting protein 3a suppresses proliferation, migration and invasion in tongue squamous cell carcinoma via the extracellular signal-regulated kinase-Snai2 pathway

Loss of MTUS1/ATIP expression is associated with adverse outcome in advanced bladder carcinomas: data from a retrospective study

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