Total Survivin and acetylated Survivin correlate with distinct molecular subtypes of breast cancer

Yakirevich, Evgeny; Samkari, Ayman; Holloway, Michael P.; Lu, Shaolei; Singh, Kamaljeet; Yu, Jovian; Fenton, Mary Anne; Altura, Rachel A.

doi:10.1016/j.humpath.2011.07.014

Cited by 11 publications

(7 citation statements)

References 41 publications

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“…We finally included 23 articles in our meta‐analysis to evaluate prognosis and clinical significance of survivin in breast cancer, in which 21 had data of HR with 95% CI (directly and indirectly), 14 had data for OR analysis (Fig. ).…”

Section: Resultsmentioning

confidence: 99%

“…In reference 28, Ryan BM used IHC to detect survivin by two difference cut‐off values (median and 25th percentile), so these four group data of HR about OS or RFS/DFS were all extracted as separate data sets for statistical analysis. In Yakirevich's and Sohn's studies, localizations of survivin were specifically reported in whole cell and also nuclear or cytoplasm of the cell, so all these data were extracted and analyzed for the correlation between survivin expression and survival of patients separately. In Younis's study, the survivin‐related survival outcomes were given in both forms of nuclear and cytoplasm localization of cell, so they were similarly extracted separately for further analysis.…”

Section: Resultsmentioning

confidence: 99%

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Prognostic Significance of Survivin in Breast Cancer: Meta-analysis

et al. 2014

Breast J

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Survivin, an inhibitor of apoptosis protein, is a potentially prognostic factor and therapeutic target in breast carcinoma, but no consensus exists based on heterogeneous data. The aim of this present study is to clarify the prognostic relevance of survivin in breast cancer patients. Relevant articles were screened in PubMed and EMBASE databases. Patients' clinical characteristics, overall survival (OS), disease/recurrence-free survival (DFS/RFS) and positive expressed survivin rates were extracted for further analysis. Statistics extracted from Kaplan-Meier survival curves were calculated indirectly with methods developed by Parmar, Williamson, and Tierney. Multivariate Cox hazard regression analysis data were used directly in Stata 11.0. Pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated to evaluate the prognostic role of survivin in breast cancer. Online literature search identified 23 articles containing 3,259 breast cancer patients. Our meta-analysis of all included studies about survival outcomes showed positive correlation between poor prognosis and survivin expression. Pooled HRs (95% CIs) for OS and DFS/RFS were 1.37 (1.12-1.68) and 1.34 (1.02-1.76), respectively. Subgroup analyses considering methods used to detect survivin (immunohistochemistry or not) and localization of survivin (whole, nuclear or cytoplasm of the cell) were also conducted, and all the above analyses supported the stability of the prognostic role of survivin. In addition, our study revealed a significant association between survivin expression and lymph node metastasis (OR: 2.74; 95% CI: 1.27-5.93) or stage of breast cancer (OR: 2.01; 95% CI: 1.29-3.13). Positive expression of survivin demonstrated a significantly higher risk of recurrence and decreased OS rates in breast cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Prognostic Significance of Survivin in Breast Cancer: Meta-analysis

et al. 2014

Breast J

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“…6 More recently the same group has suggested that monitoring the localization of acetylated survivin has diagnostic potential in breast cancer subtyping. 26,27 Using a similar mutagenic strategy to them, we investigated whether this PTM impacts on survivin function during mitotic exit. Our data clearly show that cells expressing the acetyl-mimetic, K129A, do not heed the "wait anaphase" signal, but rush through anaphase in the presence of maloriented chromosomes, resulting in aberrant division, often producing 3 aneuploid cells or binucleation.…”

Section: Discussionmentioning

confidence: 99%

Mitotic activity of survivin is regulated by acetylation at K129

2015

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Survivin is a cancer-associated protein regulated by multiple factors, including acetylation at K129 within its C-terminal a-helical tail. Acetylation of survivin is being pursued as a potential prognostic marker in breast cancer. This modification at K129 may cause nuclear accumulation of survivin in interphase cells; however, whether this affects its essential role during mitosis has not been addressed. We posited whether mimicking acetylation of survivin at K129 alters its activity during mitosis. Fluorescence microscopy and time-lapse imaging showed that, mutating this site to an alanine to act as a constitutive acetyl mimetic, K129A, causes defects in chromosome segregation and cytokinesis. As a non-acetylatable version, K129R, also has difficulty during mitotic exit, we conclude that cyclical acetylation and deacetylation is required for fully functional survivin during mitosis.

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“…It is overexpressed in breast tumor tissues, but hardly expressed in most normal tissues (Montazeri et al, 2012;Yakirevich et al, 2012). Therefore, it may be an attractive target for antitumor gene therapy.…”

Section: Discussionmentioning

confidence: 99%