期刊
JOURNAL OF CANCER
卷 10, 期 26, 页码 6635-6648出版社
IVYSPRING INT PUBL
DOI: 10.7150/jca.36125
关键词
integrin beta 4; papillary thyroid carcinoma; anoikis; lymphovascular tumor thrombus
类别
资金
- Shenzhen Health System Research Project [SZFZ2018074]
- Research Foundation of Peking University Shenzhen Hospital [JCYJ2018001]
- Open Research Fund of State Key Laboratory of Chemical Oncogenomics in 2018
- San-ming Project of Medicine in Shenzhen [SZSM20182088, SZSM201612041]
Although the majority of papillary thyroid cancers (PTC) are indolent, a subset of PTCs behaves aggressively due to extensive invasion and distant metastasis. Integrin beta 4, a member of the integrin family, has been shown to enhance the progression in some malignancies; however, its role in PTC remains unclear. Here, we demonstrated that beta 4 overexpression was associated with extrathyroid extension, lymph node metastasis, high TNM stage, and poor overall survival based on The Cancer Genome Atlas cohort. Immunohistochemistry showed that beta 4 expression was significantly upregulated in the tumors with infiltrating growth pattern, as well as those with positive lymphovascular invasion. Moreover, beta 4 was invariably overexpressed in the lymphovascular tumor thrombi, which has not been reported before. After shRNA-induced knockdown of beta 4 in vitro, the migration, invasion and scratch repair ability of the tumor cells were significantly reduced. Furthermore, beta 4 reduction decreased anchorage-independent growth and increased anoikis. The bioinformatics analysis revealed that approximately 70 pathways were significantly dysregulated in the high beta 4 expression group. The MAPK pathway and propanoate metabolism were located in the network center of those pathways. Taken together, our results suggest that beta 4 could promote the tumor's aggressiveness by enhancing invasion and antagonizing anoikis. The upregulated expression of beta 4 in the tumor thrombi is intrinsically linked to its role in strengthening the anoikis resistance.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据