Absence of AIF1L contributes to cell migration and a poor prognosis of breast cancer
Authors Liu P, Li W, Hu Y, Jiang Y
Received 19 February 2018
Accepted for publication 30 May 2018
Published 5 September 2018 Volume 2018:11 Pages 5485—5498
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Manfred Beleut
Peer reviewer comments 4
Editor who approved publication: Dr Jianmin Xu
Peipei Liu,1 Wenhui Li,2 Yuanyuan Hu,1 Youhong Jiang1
1Molecular Oncology Laboratory of Cancer Research Institute, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 2Gastrointestinal Onco-Pathology Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang 110001, People’s Republic of China
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.
Keywords: AIF1L, breast cancer, cytoskeleton, TCGA
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