IQ Motif Containing GTPase-Activating Protein 3 Is Associated with Cancer Stemness and Survival in Pancreatic Ductal Adenocarcinoma.

IF 3.5 4区 医学 Q3 CELL BIOLOGY Pathobiology Pub Date : 2024-01-01 Epub Date: 2023-12-16 DOI:10.1159/000535542
Aya Kido, Akira Ishikawa, Takafumi Fukui, Narutaka Katsuya, Kazuya Kuraoka, Kazuhiro Sentani, Sho Tazuma, Takeshi Sudo, Masahiro Serikawa, Shiro Oka, Naohide Oue, Wataru Yasui
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Abstract

Introduction: 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.

Discussion/conclusion: These results suggest that IQGAP3, a transmembrane protein, is involved in survival and stemness and may be a promising new therapeutic target for PDAC.

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含 IQ motif 的 GTPase 活化蛋白 3 与胰腺导管腺癌的癌症干性和存活率有关。
简介胰腺导管腺癌(PDAC)是最致命的恶性肿瘤之一,预后不良,发病率不断上升。IQ motif-containing GTPase-activating protein 3 (IQGAP3)是IQGAPs家族中的一种支架蛋白,可调控细胞骨架重塑和细胞信号传导等多种细胞活动。本研究旨在分析IQGAP3在PDAC中的表达和生物学功能:我们用免疫组化方法分析了81个PDAC样本中IQGAP3的表达。结果:免疫组化分析了81个PDAC样本中IQGAP3的表达,采用RNA干扰抑制IQGAP3在PDAC细胞系中的表达:结果:IQGAP3的免疫组化分析表明,54.3%的PDAC细胞质中IQGAP3表达阳性,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的分析中,IQGAP3 的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》(The Cancer Genome Atlas)数据库表明,IQGAP3 与驱动蛋白家族成员 C1(KIFC1)共定位,而我们之前曾报道 KIFC1 是一种癌症干细胞相关蛋白。通过ERK和AKT通路,IQGAP3 siRNA处理可减少PDAC细胞的增殖和球形集落的形成:这些结果表明,IQGAP3是一种跨膜蛋白,它参与生存和干细胞的形成,可能是治疗PDAC的一个有前景的新靶点。
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来源期刊
Pathobiology
Pathobiology 医学-病理学
CiteScore
8.50
自引率
0.00%
发文量
47
审稿时长
>12 weeks
期刊介绍: ''Pathobiology'' offers a valuable platform for the publication of high-quality original research into the mechanisms underlying human disease. Aiming to serve as a bridge between basic biomedical research and clinical medicine, the journal welcomes articles from scientific areas such as pathology, oncology, anatomy, virology, internal medicine, surgery, cell and molecular biology, and immunology. Published bimonthly, ''Pathobiology'' features original research papers and reviews on translational research. The journal offers the possibility to publish proceedings of meetings dedicated to one particular topic.
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