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Absence of AIF1L contributes to cell migration and a poor prognosis of breast cancer.

ABSTRACT: Background:Breast cancer is the most common fatal cancer in women worldwide. Previous studies have demonstrated that allograft inflammatory factor 1 like (AIF1L) plays a key role in mammary tumorigenesis, although the mechanism involved remains unclear. Purpose:The purpose of this study was to assess the clinicopathological and prognostic significance of AIF1L expression levels and biological function in breast cancer. Patients and methods:We used immunohistochemistry to detect the expression of AIF1L in breast cancer. We also analyzed the expression of AIF1L in breast cancer using the Cancer Genome Atlas (TCGA) cohort and the Cancer Cell Line Encyclopedia (CCLE). Furthermore, both in vitro assays were used to determine the effect of AIF1L on malignant behavior in breast cancer cells. Results:We detected AIF1L expression in tissue microarrays through immunohistochemistry and found that protein expression was significantly lower in BC tissues (28.6%, 82/287) compared to tumor-adjacent tissues (58.3%, 28/48) (P=0.007). Kaplan-Meier survival analysis revealed that disease-specific survival in BC patients with low AIF1L protein expression was significantly poorer compared to normal controls (P=0.040). In the TCGA cohort, the AIF1L gene was downregulated and hypermethylated in tumor samples compared to normal controls. Bioinformatics analysis using CCLE predicted potential biological functions of AIF1L related to tight junctions, cell junctions and focal adhesion. Ectopic expression of AIF1L suppressed MDA-MB-231 migration and invasion. Further evidence confirmed that AIF1L overexpression suppressed cell spreading, altered cell shape and decreased protrusion formation, which was correlated with decreased focal adhesion kinase (FAK) and RhoA expression. Conclusion:These findings suggest that AIF1L is a potential prognostic biomarker that plays a vital role in regulating the cytoskeleton in breast cancer.

SUBMITTER: Liu P

PROVIDER: S-EPMC6134948 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Absence of AIF1L contributes to cell migration and a poor prognosis of breast cancer.

Liu Peipei P Li Wenhui W Hu Yuanyuan Y Jiang Youhong Y

OncoTargets and therapy 20180905

<h4>Background</h4>Breast cancer is the most common fatal cancer in women worldwide. Previous studies have demonstrated that allograft inflammatory factor 1 like (AIF1L) plays a key role in mammary tumorigenesis, although the mechanism involved remains unclear.<h4>Purpose</h4>The purpose of this study was to assess the clinicopathological and prognostic significance of AIF1L expression levels and biological function in breast cancer.<h4>Patients and methods</h4>We used immunohistochemistry to de ...[more]

PMID: 30233209

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Project description:BackgroundThe expression of the immunoregulatory protein B7-H4 has been reported in many types of cancer, including breast cancer. However, its role in triple-negative breast cancer (TNBC), especially its correlation with patients' prognosis and chemoresistance remains unclear.MethodsThe expression of B7-H4 in TNBC tissues and cell lines were measured with Real-Time PCR and western blotting. 65 cases of TNBC tissue samples and adjacent non-tumor tissue samples were analyzed by immunochemistry to demonstrate the correlation between the B7-H4 expression and clinicopathological characteristics. In vitro studies assessed mAb MIH43 alone and in combination with transfecting B7-H4 siRNA on the growth of chemosensitive and chemoresistant TNBC cell lines by CCK-8 and apoptotic enzyme-linked immunosorbent assay (ELISA).ResultsB7-H4 expression was detected positive in 59 of 65 (90.8%) different stage TNBC patients, especially in the samples of recurrence TNBC patients after receiving neoadjuvant chemotherapy treatment. Survival curves showed that patients with B7-H4 overexpression had significantly shorter survival and recurrence time than those with low B7-H4 expression (p?<?0.005). Univariate and multivariate COX regression analysis demonstrated that B7-H4 was an independent predictor for advanced tumor stage. The monoclonal antibody of B7-H4 has the potential anti-proliferative effects on inhibiting the chemoresistant TNBC cell lines and increasing the sensitivity of TNBC cell lines to doxorubicin, paclitaxel or carboplatin. RNAi-mediated silencing of B7-H4 in TNBC cells enhanced drug-induced apoptosis via inhibiting PTEN/PI3K/AKT pathway, whereas reexpression of B7-H4 in B7-H4 knockdown and low B7-H4 expressing cells increased the phosphorylation of PI3K and AKT along with restoration of PETN expression.ConclusionsOur data show that B7-H4 is a biomarker indicative of a poor prognosis in TNBC patients and at least partially downregulated in chemoresistance via PTEN/PI3K/AKT pathway. Targeting B7-H4 might provide an attractive therapeutic approach specifically for TNBC patients.

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Absence of AIF1L contributes to cell migration and a poor prognosis of breast cancer.

Publications

Absence of AIF1L contributes to cell migration and a poor prognosis of breast cancer.

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