Integrin β6 serves as an immunohistochemical marker for lymph node metastasis and promotes cell invasiveness in cholangiocarcinoma.

Integrin β6 serves as an immunohistochemical marker for lymph node metastasis and promotes cell invasiveness in cholangiocarcinoma.
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DOI:
10.1038/srep30081
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发表时间:
2016-07-21
期刊:
影响因子:
4.6
通讯作者:
Niu J
Niu J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li Z;Biswas S;Liang B;Zou X;Shan L;Li Y;Fang R;Niu J

文献摘要

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胆管癌是一种毁灭性的恶性肿瘤,是出了名的难以诊断,并与高死亡率。尽管广泛的努力,以改善这种肿瘤的诊断和治疗,取得了有限的进展。整联蛋白β6是整联蛋白的一种亚型,其仅在上皮细胞表面上表达,并且与多种肿瘤相关。本研究旨在探讨整合素β6在胆管癌中的表达及其作用。胆管癌组织中β6表达上调与淋巴结转移和远处转移有关。此外,整合素β6被确定为诊断胆管癌的生物标志物和淋巴结转移的指标。整合素β6显著促进胆管癌细胞的增殖、迁移和侵袭。此外,整合素β6增加Rac 1-GT α,导致金属蛋白酶9(MMP 9)和F-肌动蛋白聚合的上调。综上所述,我们的研究结果表明,整合素β6以Rac 1依赖的方式促进肿瘤侵袭,是肿瘤转移的潜在生物标志物。整合素β6可能有助于提高诊断准确性,靶向β6可能成为胆管癌治疗的新策略。
Cholangiocarcinoma is a devastating malignancy that is notoriously difficult to diagnose and is associated with a high mortality. Despite extensive efforts to improve the diagnosis and treatment of this neoplasm, limited progress has been made. Integrin β6 is a subtype of integrin that is expressed exclusively on the surfaces of epithelial cells and is associated with a variety of tumors. In the present study, we investigated the expression and roles of integrin β6 in cholangiocarcinoma. β6 upregulation in cholangiocarcinoma was correlated with lymph node metastasis and distant metastasis. Moreover, integrin β6 was identified as a biomarker for the diagnosis of cholangiocarcinoma and an indicator of lymph node metastasis. Integrin β6 significantly promoted the proliferation, migration and invasion of cholangiocarcinoma cells. Furthermore, integrin β6 increased Rac1-GTPase, resulting in the upregulation of metalloproteinase-9 (MMP9) and F-actin polymerization. Taken together, our results indicate that integrin β6 promotes tumor invasiveness in a Rac1-dependent manner and is a potential biomarker for tumor metastasis. Integrin β6 may help to improve the diagnostic accuracy, and targeting β6 may be a novel strategy for the treatment of cholangiocarcinoma.