Tumor cell-specific AIM2 regulates growth and invasion of cutaneous squamous cell carcinoma.
Tumor cell-specific AIM2 regulates growth and invasion of cutaneous squamous cell carcinoma.
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DOI：
10.18632/oncotarget.17573
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发表时间：
2017-07-11
期刊：
影响因子：
--
通讯作者：
Kähäri VM
中科院分区：
文献类型：
--
作者：
Farshchian M;Nissinen L;Siljamäki E;Riihilä P;Piipponen M;Kivisaari A;Kallajoki M;Grénman R;Peltonen J;Peltonen S;Quint KD;Bavinck JNB;Kähäri VM
皮肤鳞状细胞癌（cSCC）是最常见的转移性皮肤癌。炎症是cSCC进展的典型特征。对cSCC细胞系和正常人表皮角质形成细胞中炎性小体组分的表达的分析揭示了cSCC细胞中AIM 2 mRNA和蛋白的表达上调。与正常皮肤相比，在体内cSCC中注意到AIM 2 mRNA水平升高。在体内散发性人cSCC中用免疫组织化学（IHC）检测到AIM 2的强和中等肿瘤细胞特异性表达，而AIM 2的表达在原位cSCC（cSCCIS）中为中等，在光化性角化病（AK）和正常皮肤中为低或不存在。来自器官移植受者的cSCC、cSCCIS和AK的IHC也显示cSCC中AM 2的强和中等肿瘤细胞特异性表达。AIM 2的敲低导致cSCC细胞的活力降低和细胞凋亡的发生。cSCC细胞中AIM 2敲低后的RNA-seq和途径分析揭示了生物功能类别细胞周期的下调和生物功能类别细胞死亡和存活的上调。AIM 2的敲低也导致cSCC细胞侵袭的减少和侵袭蛋白酶MMP 1和MMP 13的产生的下调。AIM 2的敲低导致体内cSCC异种移植物的生长和血管化受到抑制。这些结果为AIM 2在cSCC进展中的作用提供了证据，并将AIM 2炎性小体功能鉴定为这些侵袭性和转移性肿瘤中的潜在治疗靶点。
Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer. Inflammation is a typical feature in cSCC progression. Analysis of the expression of inflammasome components in cSCC cell lines and normal human epidermal keratinocytes revealed upregulation of the expression of AIM2 mRNA and protein in cSCC cells. Elevated levels of AIM2 mRNA were noted in cSCCs in vivo compared with normal skin. Strong and moderate tumor cell specific expression of AIM2 was detected with immunohistochemistry (IHC) in sporadic human cSCCs in vivo, whereas expression of AIM2 was moderate in cSCC in situ (cSCCIS) and low or absent in actinic keratosis (AK) and normal skin. IHC of cSCCs, cSCCIS and AKs from organ transplant recipients also revealed strong and moderate tumor cell specific expression of AIM2 in cSCCs. Knockdown of AIM2 resulted in reduction in viability of cSCC cells and onset of apoptosis. RNA-seq and pathway analysis after knockdown of AIM2 in cSCC cells revealed downregulation of the biofunction category Cell cycle and upregulation of the biofunction category Cell Death and Survival. Knockdown of AIM2 also resulted in reduction in invasion of cSCC cells and downregulation in production of invasion proteinases MMP1 and MMP13. Knockdown of AIM2 resulted in suppression of growth and vascularization of cSCC xenografts in vivo. These results provide evidence for the role of AIM2 in the progression of cSCC and identify AIM2 inflammasome function as a potential therapeutic target in these invasive and metastatic tumors.
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影响因子：
8
作者：
Ala-aho, R;Ahonen, M;Kähäri, VM
通讯作者：
Kähäri, VM
影响因子：
6
作者：
Farshchian, Mehdi;Kivisaari, Atte;Kahari, Veli-Matti
通讯作者：
Kahari, Veli-Matti
影响因子：
10.3
作者：
Diepgen, TL;Mahler, V
通讯作者：
Mahler, V
影响因子：
8.7
作者：
Man SM;Kanneganti TD
通讯作者：
Kanneganti TD
影响因子：
17.1
作者：
Dombrowski Y;Peric M;Koglin S;Kammerbauer C;Göss C;Anz D;Simanski M;Gläser R;Harder J;Hornung V;Gallo RL;Ruzicka T;Besch R;Schauber J
通讯作者：
Schauber J