Abstract
The epidermal growth factor (EGF) pathway plays critical roles during cancer cell epithelial-mesenchymal transition (EMT) process and metastasis. Epidermal growth factor receptor (EGFR), as one of the important receptors of EGF, undergoes autophosphorylation with the stimulation of EGF and activates MAPK/ERK, PI3K/Akt/mTOR, and other pathways. Here, we identified EGFR was a target of miR-338-5p. Upon EGF treatment, overexpression of miR-338-5p not only downregulated EGFR expression and inhibited MAPK/ERK signaling, but also inhibited EMT and metastasis process of pancreatic cancer (PC) cells. In the clinical pathological analysis, miR-338-5p was significantly down-regulated in 44 pairs PC tissues and its expression was negatively associated with lymph node metastasis and AJCC stage. Furthermore, Overexpression of EGFR partially reversed the protective effect of miR-338-5p overexpression on EGF-mediated migration and invasion in PC cells. Taken together, miR-338-5p controls EGF-mediated EMT and metastasis in PC cells by targeting EGFR/ERK pathways. Here, we hope to provide new insights into the molecular mechanisms of pancreatic cancer, and may help facilitating development of EGFR-based therapies for human cancer.
Highlights
Pancreatic ductal adenocarcinoma cancer (PDAC), the fourth leading cause of cancer-related death in the United States, remains one of the deadliest malignancies, with a 5-year survival rate of 9% [1]
We examined the expression of epidermal growth factor receptor (EGFR) protein and miR-338-5p in pancreatic cancer (PC) tissues and cell lines. found that miR-3385p was a key negative regulator of EGFR, downregulation of miR-338-5p was associated with the JACC stage and lymph node status
EGFR plays an important role in the etiology and progression of many carcinomas, including PC
Summary
Pancreatic ductal adenocarcinoma cancer (PDAC), the fourth leading cause of cancer-related death in the United States, remains one of the deadliest malignancies, with a 5-year survival rate of 9% [1]. PDAC is often diagnosed at advanced stages that are locally invasive and/or widely metastatic, which precludes the possibility for potentially curative resection. In cases that are resectable, lymph node involvement is common, and cancer cell invasion or spread into peripancreatic or distant lymph nodes is associated with increased risk of disease recurrence and a poor prognosis [2]. It has been confirmed that epithelial-mesenchymal transition (EMT) is a prominent process promoted aggressive local invasion and distant metastasis in pancreatic cancer [3]. The epidermal growth factor receptor (EGFR) family has been demonstrated to strongly affect EMT process in many types of cancer, including pancreatic [4,5,6]. In a Phase III trial, erlotinib, an EGFR tyrosine kinase inhibitor, has been proven effective
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