ROS-mediated ITGB5 promotes tongue squamous cell carcinoma metastasis through epithelial mesenchymal transition and cell adhesion signal pathway.

IF 2.7 3区 医学 Q3 ONCOLOGY Journal of Cancer Research and Clinical Oncology Pub Date : 2024-08-24 DOI:10.1007/s00432-024-05922-z
Weixiong Chen, Haojie Yang, Lei Huang, Caihong Fang, Limin Yao, Faxin Liu, Tingting Jin
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Abstract

Purpose: Integrin β5 (ITGB5) is an integrin β subunit member widely expressed in the human bodies, especially in cancer cells and tissues, which is a key factor in promoting tumor metastasis. In this study we investigated the differential expression of ITGB5 in tongue squamous cell carcinoma (TSCC), especially in those with lymph node metastasis, and revealed the possible mechanism.

Methods: The expression of ITGB5 in TSCC was analyzed by database and verified by immunohistochemistry through 135 TSCC patients' tissue sections from Sun Yat-sen Memorial Hospital and Guangzhou First People's Hospital. The relationship between ITGB5 and lymph node metastasis or prognosis was analyzed retrospectively. The effects of ITGB5 on TSCC cells were examined through knocking down or overexpression and its possible regulator and signal pathway were explored.

Results: The expression of ITGB5 in TSCC was higher than that in adjacent tissue, and the expression in patients with lymph node metastasis was higher than that in patients without lymph node metastasis. The high expression of ITGB5 predicted a worse prognosis. Knock down of ITGB5 suppressed invasion and migration of TSCC cells, while overexpression of ITGB5 contributed to invasion and migration. Reactive oxygen species (ROS) regulated epithelial mesenchymal transition (EMT), and we further verified that ROS enhanced the expression of ITGB5 to promote the metastasis of TSCC. Mechanistically, ITGB5 functions through cell adhesion signal pathway.

Conclusion: The increased expression of ITGB5 in tongue squamous cell carcinoma with lymph node metastasis may be a potential target for evaluating lymph node metastasis and worse prognosis of tongue squamous cell carcinoma. Scavenge of ROS or knock down of ITGB5 may be the strategies to overcome metastasis of TSCC.

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ROS介导的ITGB5通过上皮间质转化和细胞粘附信号通路促进舌鳞状细胞癌转移
目的:整合素β5(ITGB5)是整合素β亚基成员之一,在人体内广泛表达,尤其是在癌细胞和组织中,是促进肿瘤转移的关键因素。本研究探讨了 ITGB5 在舌鳞状细胞癌(TSCC),尤其是淋巴结转移癌中的差异表达,并揭示了其可能的机制:方法:通过数据库分析了ITGB5在TSCC中的表达情况,并通过免疫组化方法验证了来自中山大学孙逸仙纪念医院和广州市第一人民医院的135例TSCC患者的组织切片。回顾性分析了ITGB5与淋巴结转移或预后的关系。通过敲除或过表达ITGB5检测其对TSCC细胞的影响,并探讨其可能的调节因子和信号通路:结果:ITGB5在TSCC中的表达高于邻近组织,在淋巴结转移患者中的表达高于无淋巴结转移患者。ITGB5的高表达预示着较差的预后。敲除ITGB5可抑制TSCC细胞的侵袭和迁移,而ITGB5的过表达则有助于侵袭和迁移。活性氧(ROS)调控上皮间质转化(EMT),我们进一步验证了ROS增强了ITGB5的表达,从而促进了TSCC的转移。从机理上讲,ITGB5是通过细胞粘附信号通路发挥作用的:ITGB5在有淋巴结转移的舌鳞癌中的表达增加可能是评估淋巴结转移和舌鳞癌不良预后的潜在靶点。清除ROS或敲除ITGB5可能是克服TSCC转移的策略。
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来源期刊
CiteScore
4.00
自引率
2.80%
发文量
577
审稿时长
2 months
期刊介绍: The "Journal of Cancer Research and Clinical Oncology" publishes significant and up-to-date articles within the fields of experimental and clinical oncology. The journal, which is chiefly devoted to Original papers, also includes Reviews as well as Editorials and Guest editorials on current, controversial topics. The section Letters to the editors provides a forum for a rapid exchange of comments and information concerning previously published papers and topics of current interest. Meeting reports provide current information on the latest results presented at important congresses. The following fields are covered: carcinogenesis - etiology, mechanisms; molecular biology; recent developments in tumor therapy; general diagnosis; laboratory diagnosis; diagnostic and experimental pathology; oncologic surgery; and epidemiology.
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