To verify whether amyloid precursor protein (APP) affects the migration and invasion of breast cancer cell lines, and to understand its underlying mechanisms, epithelial-mesenchymal transition (EMT), the mitogen-activated protein kinase (MAPK) signaling pathway and the matrix metalloproteinase (MMP) family were investigated in MDA-MB-231, MCF-7 and BT474 human breast cancer cells. Breast cancer cell lines were transfected with plasmids containing APP coding sequences (pEGFP-n1-APP) and APP short hairpin RNA (pENTR APP shRNA). APP overexpres-sion efficiency, knockout efficiency and the expression levels of related genes were tested using reverse transcription-quantitative PCR (RT-qPCR) and western blot analyses. The effects of APP and mitogen-activated protein kinase kinase (MEK) inhibitor on cell migration and invasion were examined using Transwell assays. The results demonstrated that APP was significantly upregulated in the pEGFP-n1-APP group (P<0.05), and significantly downregulated in the pENTR APP shRNA group (P<0.05), compared with the control group. APP overexpression increased the migratory and invasive ability of human breast cancer cells (P<0.05), whereas APP silencing significantly inhibited cell migration and invasion (P<0.05). RT-qPCR and western blot analysis results suggested that APP overexpression significantly increased the expression of MMP-9, MMP-2, MMP-3, N-cadherin and vimentin (P<0.05). In addition, the enhanced expression of APP markedly affected the phosphorylation of mitogen-activated protein kinase kinase kinase 11 (MLK3), mitogen-activated protein kinase kinase 4 (MEK4) and mitogen-activated protein kinase 10 (JNK3; P<0.05). Additionally, APP overexpression had no effect on the total expression levels of MLK3, MEK4, and JNK3; however, APP overexpression significantly decreased the expression levels of E-cadherin and cytokeratin (P<0.05). Conversely, APP silencing had the opposite effects. When cells were treated with the MEK inhibitor PD0325901, the expression of APP was not altered, nor was the expression levels of MEK and its upstream signaling molecules. Taken together, the present findings suggested that APP could affect the migration and invasion of human breast cancer cells by mediating the activation of the MAPK signaling pathway, thereby promoting the EMT process.

Emerging evidences suggest that long noncoding RNA (lncRNA) plays a vital role in tumorigenesis and cancer progression. Here, the aim of this study is to investigate the biological function of long intervening noncoding RNA Linc00284 in colorectal cancer (CRC). The expression levels of Linc00284, miR-27a and c-Met were evaluated by qPCR and/or Western blotting. Immunohistochemistry was used to detect the expression of Ki67 and Phh3 in tumor tissues. The interaction between Linc00284, miR-27a and c-Met was validated by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Cell function experiments, including CCK-8, wound-healing and transwell invasion assays, were conducted. The in vivo studies were performed with the subcutaneous tumor xenograft mouse models. Our findings reveal that Linc00284 is upregulated in CRC tissues and colorectal cancer cell lines HCT116 and SW480 in comparison with corresponding para-carcinoma tissues and human fetal colonic mucosa cells FHC. High expression of Linc00284 in tumor tissues is associated with tumor metastasis and predicts a poor clinical outcome in CRC patients. Serum Linc00284 is increased, while miR-27a is decreased in CRC patients compared to healthy controls. ROC curve analysis indicates that serum Linc00284 and miR-27a produce the area under the curve (AUC) value of at 0.8151 and 0.7316 in patients with colorectal cancer compared to healthy individuals, respectively. Additionally, results in vitro and in vivo experiments suggest that Linc00284 silencing significantly suppresses CRC cell proliferation and/or invasion. Mechanistically, Linc00284 promotes c-Met expression by acting as miR-27a sponge, leading to the activation of downstream signaling pathways, thereby causing malignant phenotypes of CRC cells. Taken together, Linc00284 exhibits oncogenic function and the disturbance of Linc00284/miR-27a/c-Met regulatory axis contributes to CRC progression, providing new insight into the pathogenesis of colorectal cancer. Importantly, the expression levels of serum Linc00284 and miR-27a may serve as clinical biomarkers for CRC diagnosis.

The WW domain is composed of 38 to 40 semi-conserved amino acids shared with structural, regulatory, and signaling proteins. WW domain-binding protein 2 (WBP2), as a binding partner of WW domain protein, interacts with several WW-domain-containing proteins, such as Yes kinase-associated protein (Yap), paired box gene 8 (Pax8), WW-domain-containing transcription regulator protein 1 (TAZ), and WW-domain-containing oxidoreductase (WWOX) through its PPxY motifs within C-terminal region, and further triggers the downstream signaling pathway in vitro and in vivo. Studies have confirmed that phosphorylated form of WBP2 can move into nuclei and activate the transcription of estrogen receptor (ER) and progesterone receptor (PR), whose expression were the indicators of breast cancer development, indicating that WBP2 may participate in the progression of breast cancer. Both overexpression of WBP2 and activation of tyrosine phosphorylation upregulate the signal cascades in the cross-regulation of the Wnt and ER signaling pathways in breast cancer. Following the binding of WBP2 to the WW domain region of TAZ which can accelerate migration, invasion and is required for the transformed phenotypes of breast cancer cells, the transformation of epithelial to mesenchymal of MCF10A is activated, suggesting that WBP2 is a key player in regulating cell migration. When WBP2 binds with WWOX, a tumor suppressor, ER transactivation and tumor growth can be suppressed. Thus, WBP2 may serve as a molecular on/off switch that controls the crosstalk between E2, WWOX, Wnt, TAZ, and other oncogenic signaling pathways. This review interprets the relationship between WBP2 and breast cancer, and provides comprehensive views about the function of WBP2 in the regulation of the pathogenesis of breast cancer and endocrine therapy in breast cancer treatment.