Blockade of integrin α3 attenuates human pancreatic cancer via inhibition of EGFR signalling

Scientific Reports
Jungwhoi LeeJae Hoon Kim

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.

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Datasets Mentioned

BETA
GSE17891
GSE79668
GSE79688

Methods Mentioned

BETA
transfection
xenograft
xenografts
enzyme-linked immunosorbent assay
PCR

Software Mentioned

GraphPad Prism
ImageJ
SPSS

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