PDF(Pubmed)
Abstract：
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of malignancy, with poor prognosis and rising incidence. IQ motif containing GTPase-activating protein 3 (IQGAP3) is a member of the IQGAPs family of scaffolding proteins that govern multiple cellular activities like cytoskeletal remodeling and cellular signal transduction. This study aimed to analyze the expression and biological function of IQGAP3 in PDAC.
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.
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.
摘要：
背景：胰腺导管腺癌（PDAC）是最致命的恶性肿瘤之一，预后差，发病率上升。含IQ基序的GTPase激活蛋白3（IQGAP3）是支架蛋白IQGAP家族的成员，该支架蛋白控制多种细胞活动，例如细胞骨架重塑和细胞信号转导。本研究旨在分析IQGAP3在PDAC中的表达及其生物学功能。
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。
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。
