Abstract
The LIM protein Ajuba has been implicated in the development of human cancers. To date, its expression pattern and biological significance in breast cancers (BC) have not been fully investigated. In the current study, we examined Ajuba protein levels in 93 invasive ductal carcinoma specimens by immunohistochemistry. The Ajuba expression level was elevated in breast cancer tissue compared with normal tissue. Ajuba overexpression is correlated with advanced tumor-node-metastasis (TNM) stage, positive node status, and adverse patient outcomes. The Ajuba protein level was also higher in BC cell lines compared to normal breast epithelial cell line MCF-10A. Ectopically expressed Ajuba in MCF-7 cells stimulated in vitro and in vivo cell growth, invasion, cell cycle progression, and decreased paclitaxel-induced apoptosis. RNA-sequencing (RNA-seq) followed by gene set enrichment analysis (GSEA) analysis showed that Ajuba overexpression regulated the Hippo signaling pathway. Ajuba overexpression also increased glucose uptake and increased expression of TAZ, GLUT3, and Survivin. TAZ knockdown abolished the role of Ajuba on GLUT3 and Survivin induction. The ChIP assay showed that TEAD4, a major TAZ binding transcription factor, could bind to the GLUT3 and Survivin promoter regions. In conclusion, our data demonstrated that elevated Ajuba expression is correlated with poor BC prognosis and regulated malignant behavior through TAZ-GLUT3/Survivin signaling in BC cells.
Highlights
Breast cancer (BC) is one of the most commonly diagnosed cancers and the second leading cause of cancer-related deaths in women [1–4]
Ajuba protein levels were examined in 93 invasive ductal carcinoma (IDC) samples and 15 normal breast tissue samples by immunohistochemistry (IHC)
Ajuba overexpression was found in 51/93 human breast cancer specimens and positively associated with TNM stage, lymph node metastasis, and poor prognosis
Summary
Breast cancer (BC) is one of the most commonly diagnosed cancers and the second leading cause of cancer-related deaths in women [1–4]. The development of novel therapeutic treatments has reduced mortality and improved the survival of breast cancer [5]. It has been reported that Ajuba is involved in the development of various human cancers. Ajuba expression is increased in cervical cancer [15], esophageal squamous cell carcinoma (ESCC) [16], colorectal cancer (CRC) [17, 18], gastric cancer [19], and pancreatic cancer [20]. Ajuba promotes cell proliferation in CRC and pancreatic cancer cells [17, 21]. Ajuba promotes ESCC cell invasion by activating ERK1/2 [16]. Growing evidence suggests that Ajuba acts as an oncogene to promote tumorigenesis, several studies reported Ajuba could function as a tumor suppressor [23, 24]. The expression pattern and biological functions of Ajuba in human breast cancers have not been fully elucidated
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