Department of Applied Life Science, SARI, Jeju National University, Jeju-do, 690-756, Republic of Korea.
Department of Bio and Brain Engineering, KAIST, Daejeon, 34141, Republic of Korea.
Sci Rep. 2019 Feb 26;9(1):2793. doi: 10.1038/s41598-019-39628-x.
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.
尽管不断做出巨大努力,胰腺癌的预后仍然不容乐观。整合素 (ITGs) 在各种恶性肿瘤中高度表达。然而,很少有研究调查整合素 α3 (ITGα3) 在恶性肿瘤中的作用。在这里,我们确定了 ITGα3 在胰腺癌中的功能作用。公共微阵列数据库分析和 Western blot 分析表明 ITGα3 在人胰腺癌细胞中独特表达。沉默 ITGα3 的表达显著抑制人胰腺癌细胞的活力和迁移。值得注意的是,与转染对照-siRNA 相比,通过增加富含亮氨酸重复和免疫球蛋白样结构域蛋白 1 (LRIG1) 的表达,ITGα3 表达的缺失导致表皮生长因子受体 (EGFR) 的表达显著降低。此外,在体内通过阻断 EGFR 信号通路,抑制 ITGα3 的表达可抑制肿瘤生长。此外,高表达的 ITGα3 导致胰腺癌患者预后不良。我们的研究结果为 ITGα3 诱导的侵袭性胰腺癌提供了新的见解。