Abstract
The prognosis of pancreatic cancer remains dismal despite continuous and considerable efforts. Integrins (ITGs) are highly expressed in various malignant cancers. However, very few studies investigated the role of integrin α3 (ITGα3) in malignant cancers. Here, we determined the functional role of ITGα3 in pancreatic cancer. Analysis of public microarray databases and Western blot analysis indicated a unique expression of ITGα3 in human pancreatic cancer. Silencing ITGα3 expression significantly inhibited the viability and migration of human pancreatic cancer cells. Notably, ablation of ITGα3 expression resulted in a significant decrease of epidermal growth factor receptor (EGFR) expression compared with transfection of control-siRNA through an increased number of leucine-rich repeats and immunoglobulin-like domain protein 1 (LRIG1) expression. In addition, ablating ITGα3 inhibited tumour growth via blockade of EGFR signalling in vivo. Furthermore, the highly expressed ITGα3 led to a poor prognosis of pancreatic cancer patients. Our results provide novel insights into ITGα3-induced aggressive pancreatic cancer.
Highlights
Pancreatic cancer is one of the most dangerous malignancies of the digestive system characterized by rapid progression, natural invasion, and grave patient outcome[1,2]
The predominant effects of negative signalling against epidermal growth factor receptor (EGFR) in mammals prevailed for a long time, mediated by inducible feedback inhibitors (IFIs) such as leucine-rich repeats and immunoglobulin-like domain protein 1 (LRIG1), receptor-associated late transducer (RALT), suppressor of cytokine signalling 4 (SOCS4), and suppressor of cytokine signalling 5 (SOCS5) that act promptly without the need for de novo protein synthesis[14,15]
We provide robust evidences suggesting that integrin α3 (ITGα3) is critical for pancreatic malignancy via coordination with EGFR signalling pathway involved in alteration of LRIG1 expression
Summary
Pancreatic cancer is one of the most dangerous malignancies of the digestive system characterized by rapid progression, natural invasion, and grave patient outcome[1,2]. Our current in silico study and another previous report suggest that ITGα3 plays a significant role in adverse prognosis of pancreatic cancer[8,9]. The predominant effects of negative signalling against EGFR in mammals prevailed for a long time, mediated by inducible feedback inhibitors (IFIs) such as leucine-rich repeats and immunoglobulin-like domain protein 1 (LRIG1), receptor-associated late transducer (RALT), suppressor of cytokine signalling 4 (SOCS4), and suppressor of cytokine signalling 5 (SOCS5) that act promptly without the need for de novo protein synthesis[14,15]. We provide robust evidences suggesting that ITGα3 is critical for pancreatic malignancy via coordination with EGFR signalling pathway involved in alteration of LRIG1 expression. Our results establish a rationale for ITGα3 as a promising therapeutic target in patients with pancreatic cancer
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