Activated spleen tyrosine kinase promotes malignant progression of oral squamous cell carcinoma via mTOR/S6 signaling pathway in an ERK1/2-independent manner.
Activated spleen tyrosine kinase promotes malignant progression of oral squamous cell carcinoma via mTOR/S6 signaling pathway in an ERK1/2-independent manner.
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激活的脾酪氨酸激酶通过mTOR/S6信号通路以ERK1/2独立的方式促进口腔鳞状细胞癌的恶性进展
DOI：
10.18632/oncotarget.19911
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发表时间：
2017-10-13
期刊：
影响因子：
--
通讯作者：
Li C
中科院分区：
文献类型：
--
作者：
Gao P;Qiao X;Sun H;Huang Y;Lin J;Li L;Wang X;Li C
脾酪氨酸激酶（SYK）是一种非受体的胞质酪氨酸酶，它通过免疫受体参与某些途径。最近，SYK在癌症中的作用已被广泛研究。SYK作为肿瘤抑制剂和肿瘤促进剂发挥双重作用。然而，其在口腔鳞状细胞癌（OSCC）中的作用尚未得到充分研究。在本研究中，收集了来自OSCC肿瘤和邻近正常对应物的样品，并通过实时qPCR评估SYK表达。SYK mRNA在肿瘤组织中的表达高于正常组织。免疫组化分析证实SYK高表达与总生存率下降密切相关。4株OSCC细胞中有2株细胞表达SYK mRNA和蛋白。SYK药理学抑制和RNAi介导的敲低通过降低磷酸化ERK 1/2和mTOR水平抑制SYK阳性细胞的增殖、迁移和侵袭。MEK的一种抑制剂PD 98059也通过减少磷酸化ERK 1/2但增加磷酸化mTOR来抑制SYK阳性细胞的相同癌症相关表型。Piceatannol，一种SYK的药理学抑制剂，在体内减弱肿瘤生长。总的来说，我们的研究结果揭示了一种新的机制引发SYK增加OSCC肿瘤发生和肿瘤进展。
Spleen tyrosine kinase (SYK), a non-receptor cytoplasmic tyrosine enzyme, is well known for its ability in certain pathways through immune receptors. Recently, SYK role in cancer has been widely studied. SYK plays a dual role as a tumor suppressor and tumor promoter. Nevertheless, its role in oral squamous cell carcinoma (OSCC) has not been fully investigated. In the current study, samples from OSCC tumors and adjacent normal counterparts were collected and SYK expression was evaluated by real-time qPCR. SYK mRNA expression in tumors was higher than the normal tissues. And high SYK expression was confirmed by immunohistochemistry analysis and closely related to worse overall survival. The expression of SYK mRNA and protein was detected in 2 of 4 OSCC cell lines. SYK pharmacological suppression and RNAi-mediated knockdown inhibited proliferation, migration, and invasion of SYK-positive cells by reducing phosphorylated ERK1/2 and mTOR levels. One inhibitor of MEK, PD98059, also suppressed the same cancer-associated phenotypes of SYK-positive cells by decreasing phosphorylated ERK1/2 but increasing phosphorylated mTOR. Piceatannol, one pharmacological inhibitor of SYK, attenuated tumor growth in vivo. Overall, our results revealed a novel mechanism triggered by SYK to increase OSCC tumoriogenesis and tumor progression.
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影响因子：
3.7
作者：
Müller R;Misund K;Holien T;Bachke S;Gilljam KM;Våtsveen TK;Rø TB;Bellacchio E;Sundan A;Otterlei M
通讯作者：
Otterlei M
影响因子：
6.4
作者：
Ogane, Satoru;Oncla, Takeshi;Shibahara, Takahiko
通讯作者：
Shibahara, Takahiko
影响因子：
20.3
作者：
Leseux, Ludivine;Hamdi, Safouane M.;Bezombes, Christine
通讯作者：
Bezombes, Christine
影响因子：
2.8
作者：
Dias, Steven J.;Li, Kun;Levenson, Anait S.
通讯作者：
Levenson, Anait S.
DOI：
10.1073/pnas.0401602101
发表时间：
2004-04-20
影响因子：
11.1
作者：
Mócsai, A;Humphrey, MB;Nakamura, MC
通讯作者：
Nakamura, MC