Abstract
BackgroundAnillin (ANLN), an actin-binding protein required for cytokinesis, has recently been presented as part of a prognostic marker panel in breast cancer. The objective of the current study was to further explore the prognostic and functional value of ANLN as a single biomarker in breast cancer.MethodsImmunohistochemical assessment of ANLN protein expression was performed in two well characterized breast cancer cohorts (n = 484) with long-term clinical follow-up data and the results were further validated at the mRNA level in a publicly available transcriptomics dataset. The functional relevance of ANLN was investigated in two breast cancer cell lines using RNA interference.ResultsHigh nuclear fraction of ANLN in breast tumor cells was significantly associated with large tumor size, high histological grade, high proliferation rate, hormone receptor negative tumors and poor prognosis in both examined cohorts. Multivariable analysis showed that the association between ANLN and survival was significantly independent of age in cohort I and significantly independent of proliferation, as assessed by Ki-67 expression in tumor cells, age, tumor size, ER and PR status, HER2 status and nodal status in cohort II. Analysis of ANLN mRNA expression confirmed that high expression of ANLN was significantly correlated to poor overall survival in breast cancer patients. Consistent with the role of ANLN during cytokinesis, transient knock-down of ANLN protein expression in breast cancer cell lines resulted in an increase of senescent cells and an accumulation of cells in the G2/M phase of the cell cycle with altered cell morphology including large, poly-nucleated cells. Moreover, ANLN siRNA knockdown also resulted in decreased expression of cyclins D1, A2 and B1.ConclusionsANLN expression in breast cancer cells plays an important role during cell division and a high fraction of nuclear ANLN expression in tumor cells is correlated to poor prognosis in breast cancer patients, independent of Ki-67, tumor size, hormone receptor status, HER2 status, nodal status and age.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2923-8) contains supplementary material, which is available to authorized users.
Highlights
Anillin (ANLN), an actin-binding protein required for cytokinesis, has recently been presented as part of a prognostic marker panel in breast cancer
Nuclear fraction of ANLN expression is significantly associated with clinicopathological parameters To validate the relevance of ANLN as a prognostic marker in breast cancer, ANLN protein expression was analyzed in two independent Tissue microarray (TMA) cohorts comprising of 144
In conclusion, our data shows that ANLN expression is a strong prognostic factor in breast cancer and essential for cell cycle progression
Summary
Anillin (ANLN), an actin-binding protein required for cytokinesis, has recently been presented as part of a prognostic marker panel in breast cancer. The objective of the current study was to further explore the prognostic and functional value of ANLN as a single biomarker in breast cancer. Breast cancer is the most common female malignancy world-wide and approximately 500 000 women succumb to the disease annually [1]. The actin-binding protein ANLN is a ubiquitously expressed protein required for cytokinesis. ANLN interacts closely with RhoA, stabilizes the localization of the latter to the cleavage furrow and stimulates the expression of active RhoA [4, 6]. Numerous additional proteins, including F-actin, myosin, septins and CD2AP have been shown to interact with ANLN during assembly, maintenance and ingression of the cleavage furrow [7]. Lack of ANLN is generally associated with correct assembly of the cleavage furrow but deficiencies during furrow ingression and completion of cell separation [3, 5]
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