Upregulation of OTUD7B (Cezanne) Promotes Tumor Progression via AKT/VEGF Pathway in Lung Squamous Carcinoma and Adenocarcinoma
Upregulation of OTUD7B (Cezanne) Promotes Tumor Progression via AKT/VEGF Pathway in Lung Squamous Carcinoma and Adenocarcinoma
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肺鳞癌和腺癌中 OTUD7B (Cezanne) 的上调通过 AKT/VEGF 途径促进肿瘤进展
DOI：
10.3389/fonc.2019.00862
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发表时间：
2019-09-11
影响因子：
4.7
通讯作者：
Shi, Jian-hong
中科院分区：
文献类型：
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作者：
Lin, Dan-dan;Shen, Yang;Shi, Jian-hong
OTUD7B是一种多功能去泛素化酶，在炎症和增殖信号中起重要作用。然而，它在肺癌中的作用在很大程度上仍然未知。本研究的目的是评估OTUD7B在肺腺癌和鳞癌患者中的预后意义，并探讨其在肺癌进展和转移中的分子机制。纳入两组包含150对肺鳞癌和匹配的邻近非癌组织的组织微阵列，以及一组包含75对肺腺癌和邻近非癌组织的组织微阵列，并进行免疫组化染色，评估OTUD7B在非小细胞肺癌中的临床相关性。OTUD7B在肺鳞癌和腺癌中均高表达，并与较差的预后相关。NCI-H358和A549细胞系的MTT增殖、集落形成、迁移和侵袭实验及免疫印迹实验表明，OTUD7B增强egf诱导的Akt信号转导，促进肺癌细胞的增殖和迁移。171例大尺度肺癌患者免疫组化染色显示OTUD7B与VEGF表达呈正相关。ELISA和成管实验显示OTUD7B促进VEGF生成和血管生成。NCI-H358肿瘤模型表明，OTUD7B通过促进Akt信号的激活，是肺肿瘤进展所必需的。这些发现共同确定了OTUD7B是非小细胞肺癌预后的独立预测因子，揭示了OTUD7B通过Akt/VEGF信号通路促进肺癌细胞增殖和转移。
OTUD7B, a multifunctional deubiquitinylase, plays an essential role in inflammation and proliferation signals. However, its function in lung cancer remains largely unknown. The aim of this study was to evaluate the prognostic significance of OTUD7B in patients with lung adenocarcinoma and squamous carcinoma and to characterize its molecular mechanisms in lung cancer progression and metastasis. Two tissue microarrays containing 150 pairs of lung squamous carcinoma and matched adjacent non-cancer tissues, and one tissue microarray containing 75 pairs of lung adenocarcinoma and adjacent non-cancer tissues were included, and immunohistochemical staining was performed to assess the clinical relevance of OTUD7B in non-small cell lung cancer. OTUD7B is highly expressed in both lung squamous carcinoma and adenocarcinoma and correlates with a worse prognosis. MTT proliferation, colony formation, migration and invasion assays and immunoblotting assay in NCI-H358 and A549 cell lines suggested that OTUD7B enhances EGF-induced Akt signal transduction and promotes lung cancer cell proliferation and migration. Immunohistochemical staining of large-scale lung cancer subjects (171 cases) revealed positive correlation of OTUD7B and VEGF expression. ELISA and tube formation assay revealed OTUD7B promotes VEGF production and angiogenesis. NCI-H358 tumor model demonstrated OTUD7B is required for lung tumor progression by facilitating activation of Akt signaling. These findings collectively identified OTUD7B as an independent predictive factor for the prognosis of non-small cell lung cancer and revealed OTUD7B promotes lung cancer cell proliferation and metastasis via Akt/VEGF signal pathway.