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XBP1 促进肿瘤侵袭,与口腔鳞状细胞癌的不良预后相关。

XBP1 promotes tumor invasion and is associated with poor prognosis in oral squamous cell carcinoma.

机构信息

Key Lab for Oral Biomedical Engineering of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079, P.R. China.

Department of Oral Histopathology, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079, P.R. China.

出版信息

Oncol Rep. 2018 Aug;40(2):988-998. doi: 10.3892/or.2018.6498. Epub 2018 Jun 18.

Abstract

X‑box‑binding protein 1 (XBP1) contributes to various types of cancer including breast, bladder cancer and esophageal squamous cell carcinoma. The aim of the study was to examine the metastatic role of XBP1 in oral squamous cell carcinoma (OSCC), and identify possible downstream molecules. Immunohistochemical staining was conducted on tissue microarrays comprising 96 OSCC cases to determine the expression level of XBP1 and analyze its association with metastasis, clinicopathological characteristics and survival prognosis. Compared with the adjacent normal tissues of OSCC, the expression of XBP1 was significantly increased in the tumor center and front area, and lymph nodes metastases (P<0.05). A relatively high XBP1 expression was associated with histological grades (P<0.05), advanced clinical stages (P<0.05), unfavorable 5‑year survival (P=0.027). Suppressed XBP1 expression caused a significant reduction of cell invasion capability (P<0.05). AXL and the downstream molecules, such as PI3K, MMP1, MMP3, and uPA were significantly suppressed when XBP1 expression was inhibited in OSCC cells. Once XBP1 was activated by Thapsigargin, AXL expression was restored. Moreover, aberrant AXL expression was associated with XBP1 overexpression in OSCC tissues (P<0.05). In conclusion, XBP1 is a potential target that is relevant to suppressing cell invasion and is associated with patient prognosis in OSCC.

摘要

X 盒结合蛋白 1(XBP1)有助于多种类型的癌症,包括乳腺癌、膀胱癌和食管鳞状细胞癌。本研究旨在研究 XBP1 在口腔鳞状细胞癌(OSCC)中的转移作用,并鉴定可能的下游分子。使用包含 96 例 OSCC 病例的组织微阵列进行免疫组织化学染色,以确定 XBP1 的表达水平,并分析其与转移、临床病理特征和生存预后的关系。与 OSCC 的相邻正常组织相比,XBP1 在肿瘤中心和前缘以及淋巴结转移中的表达显著增加(P<0.05)。相对较高的 XBP1 表达与组织学分级(P<0.05)、晚期临床分期(P<0.05)、不良的 5 年生存率(P=0.027)相关。抑制 XBP1 的表达导致细胞侵袭能力显著降低(P<0.05)。当 OSCC 细胞中抑制 XBP1 的表达时,AXL 和下游分子,如 PI3K、MMP1、MMP3 和 uPA,显著受到抑制。一旦 XBP1 被 Thapsigargin 激活,AXL 的表达就会恢复。此外,AXL 的异常表达与 OSCC 组织中 XBP1 的过表达相关(P<0.05)。总之,XBP1 是一个潜在的靶点,与抑制细胞侵袭有关,并与 OSCC 患者的预后相关。

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