METHODS: We analyzed IQGAP3 expression in 81 PDAC samples by immunohistochemistry. RNA interference was used to inhibit IQGAP3 expression in PDAC cell lines.
RESULTS: Immunohistochemical analysis of IQGAP3 showed that 54.3% of PDACs were positive for cytoplasmic expression of IQGAP3, with no expression found in non-neoplastic tissue. Furthermore, IQGAP3 expression was an independent poor prognostic factor in our immunostaining-based studies and analyses of public databases. Our cohort and the Cancer Genome Atlas database indicated that IQGAP3 is co-localized with kinesin family member C1 (KIFC1), which we previously reported as a cancer stem cell-associated protein. IQGAP3 small interfering RNA treatment decreased PDAC cell proliferation and spheroid colony formation via ERK and AKT pathways.
CONCLUSIONS: These results suggest that IQGAP3, a transmembrane protein, is involved in survival and stemness and may be a promising new therapeutic target for PDAC.
方法:我们通过免疫组织化学分析了81个PDAC样品中的IQGAP3表达。RNA干扰用于抑制IQGAP3在PDAC细胞系中的表达。
结果:IQGAP3免疫组织化学分析显示,54.3%的PDACs胞浆IQGAP3阳性表达,在非肿瘤组织中无表达。此外,在我们基于免疫染色的研究和公共数据库分析中,IQGAP3表达是一个独立的不良预后因素。我们的队列和癌症基因组图谱数据库表明IQGAP3与驱动蛋白家族成员C1(KIFC1)共定位,我们以前报道的一种癌症干细胞相关蛋白。IQGAP3siRNA处理通过ERK和AKT途径降低PDAC细胞增殖和球体集落形成。
结论:这些结果表明IQGAP3,一种跨膜蛋白,与生存和干性有关,可能是PDAC有希望的新治疗靶点。