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整合素β1通过靶向CD147调节喉癌细胞的侵袭和放射抗性。

Integrin β1 regulates the invasion and radioresistance of laryngeal cancer cells by targeting CD147.

作者信息

Li Li, Dong Xiaoxia, Peng Feng, Shen Li

机构信息

1The Functional Science Laboratory, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, 442000 Hubei People's Republic of China.

2Department of Pharmacology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, 442000 Hubei People's Republic of China.

出版信息

Cancer Cell Int. 2018 Jun 7;18:80. doi: 10.1186/s12935-018-0578-z. eCollection 2018.

DOI:10.1186/s12935-018-0578-z
PMID:29930482
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5992723/
Abstract

BACKGROUND

Increased expression of integrin β1 has been reported to correlate with progression and therapy resistance in many types of cancers. The aim of this study was to investigate the effects of integrin β1 on the invasion and radioresistance of laryngeal cancer cells.

METHODS

The expression of integrin β1 in the tumor specimens of laryngeal cancer patients was assessed by immunohistochemical assays. The invasion ability of laryngeal cancer cells was detected by transwell and wound healing assays. The radiosensitivity of laryngeal cancer cells was evaluated by flow cytometry and colony formation assays.

RESULTS

High expression of integrin β1 was significantly associated with lymph node metastasis, TNM stage and poor clinical outcomes (all < 0.05). Knockdown of integrin β1 in laryngeal cancer cells inhibited invasion and increased radiosensitivity. Mechanistically, these effects were caused by suppression of the downstream focal adhesion kinase (FAK)/cortactin pathway. In addition, integrin β1 could interact with CD147 and the antibody blockade of CD147 led to the deactivation of FAK/cortactin signaling. Further studies revealed that the interaction between integrin β1 and CD147 relied on intact lipid rafts. Disruption of lipid rafts by methyl beta cyclodextrin in laryngeal cancer cells was able to reverse integrin β1-mediated malignant phenotypes.

CONCLUSIONS

Integrin β1 has potential as a therapeutic target in prevention and treatment of laryngeal cancer.

摘要

背景

据报道，整合素β1表达增加与多种癌症的进展和治疗耐药性相关。本研究旨在探讨整合素β1对喉癌细胞侵袭和放射抗性的影响。

方法

采用免疫组织化学分析评估喉癌患者肿瘤标本中整合素β1的表达。通过Transwell和伤口愈合试验检测喉癌细胞的侵袭能力。通过流式细胞术和集落形成试验评估喉癌细胞的放射敏感性。

结果

整合素β1的高表达与淋巴结转移、TNM分期及不良临床结局显著相关（均<0.05）。敲低喉癌细胞中的整合素β1可抑制侵袭并提高放射敏感性。机制上，这些作用是由下游粘着斑激酶（FAK）/皮层肌动蛋白通路的抑制引起的。此外，整合素β1可与CD147相互作用，CD147的抗体阻断导致FAK/皮层肌动蛋白信号失活。进一步研究表明，整合素β1与CD147之间的相互作用依赖于完整的脂筏。用甲基β环糊精破坏喉癌细胞中的脂筏能够逆转整合素β1介导的恶性表型。

结论

整合素β1在喉癌的预防和治疗中具有作为治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d450/5992723/67dd7c4bd1b5/12935_2018_578_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d450/5992723/a31f0063eb0b/12935_2018_578_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d450/5992723/37026437b46f/12935_2018_578_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d450/5992723/63c67b828982/12935_2018_578_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d450/5992723/6cbd6ee1c358/12935_2018_578_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d450/5992723/d28b00af96d6/12935_2018_578_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d450/5992723/2d0297763689/12935_2018_578_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d450/5992723/67dd7c4bd1b5/12935_2018_578_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d450/5992723/a31f0063eb0b/12935_2018_578_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d450/5992723/37026437b46f/12935_2018_578_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d450/5992723/63c67b828982/12935_2018_578_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d450/5992723/6cbd6ee1c358/12935_2018_578_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d450/5992723/d28b00af96d6/12935_2018_578_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d450/5992723/2d0297763689/12935_2018_578_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d450/5992723/67dd7c4bd1b5/12935_2018_578_Fig7_HTML.jpg

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