ANGPTL4 overexpression inhibits tumor cell adhesion and migration and predicts favorable prognosis of triple-negative br
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RESEARCH ARTICLE
Open Access
ANGPTL4 overexpression inhibits tumor cell adhesion and migration and predicts favorable prognosis of triple-negative breast cancer Yu-Chen Cai1†, Hang Yang1,2†, Ke-Feng Wang3, Tan-Huan Chen4, Wen-Qi Jiang1,2* and Yan-Xia Shi1,2*
Abstract Background: Triple-negative breast cancer (TNBC) patients have relatively poor clinical outcomes. A marker predicting the prognosis of patients with TNBC could help guide treatment. Extensive evidence demonstrates that angiopoietin-like 4 (ANGPTL4) is involved in the regulation of cancer growth, metastasis and angiogenesis. Therefore, its role in TNBC is of interest. Methods: We tested the ANGPTL4 expression level in tumor tissues by immunohistochemistry (IHC) and detected its association with the clinical features of TNBC patients. Next, the effects and mechanisms of ANGPTL4 on TNBC cell migration and adhesion were investigated. Results: We found that ANGPTL4 overexpression was associated with favorable outcomes in TNBC patients. ANGPTL4 upregulation inhibited cell adhesion, migration and invasion in vitro. Further analyses demonstrated that the possible mechanism might involve suppression of TNBC progression by interacting with extracellular matrix-related genes. Conclusions: The present findings demonstrated that enhancement of ANGPTL4 expression might inversely correlate with TNBC progression. ANGPTL4 is a promising marker of TNBC and should be evaluated in further studies. Trial registration: Retrospectively registered. Keywords: Triple negative breast Cancer, ANGPTL4, Prognosis, Migration, Adhesion
Background Human breast cancer is the most common cancer in women worldwide and remains a global health problem [1, 2]. This disease is a heterogeneous neoplasm with various histological characteristics, molecular phenotypes, clinical characteristics and responses to therapy. Triple-negative breast cancer (TNBC) is a type of breast malignancy that is negative for the expression of * Correspondence: [email protected]; [email protected] † Yu-Chen Cai and Hang Yang contributed equally to this work. 1 Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, People’s Republic of China Full list of author information is available at the end of the article
estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) [3, 4]. Patients with TNBC tends to present younger than other patients and have relatively aggressive clinical features [3, 5–7]. TNBC tumors are more sensitive to chemotherapy than other tumor types [3, 7] but cannot be treated with hormone therapies or drugs aimed at HER2; hence, there is a sharp decrease in survival compared with that of patients with hormonal receptor- or HER2-positive tumors [3]. Thus, improving the outcome of TNBC is a challenge in current clinical practice. A previous study demonstrated that angiopoietin-like 4 (ANGPTL4) is a HIF-1 target gene that contributes to
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