Cheuk Isabella Wai-Yin, Siu Man Ting, Ho John Chi-Wang, Chen Jiawei, Shin Vivian Yvonne, Kwong Ava
Department of Surgery, The University of Hong Kong Hong Kong SAR, China.
Department of Surgery, The University of Hong Kong-Shenzhen Hospital Hong Kong SAR, China.
Am J Cancer Res. 2020 Jan 1;10(1):211-223. eCollection 2020.
During tumorigenesis and metastasis, integrins regulate localization and activity of proteolytic enzymes that remodel the extracellular matrix. Previous studies have demonstrated blocking of αβ to effectively inhibit proliferation, angiogenesis, and the survival of various cancer cell types. However, little is known about the functional role of the integrin subunit alpha-V gene () in metastatic breast cancer. In this study, knockdown was used to identify the molecular mechanism by which promotes tumorigenesis, metastasis, proliferation, invasion, and cellular self-renewal. The effectiveness of an ITGAV antagonist, cilengitide, for breast cancer treatment was investigated . Analysis of publicly available data demonstrated that overexpression of was associated with poor relapse free survival of breast cancer patients. Silencing of inhibited cell proliferation, invasion, and self-renewal of breast cancer cell lines by altering expression of and . The use of cilengitide significantly reduced lung metastasis in a metastatic breast cancer animal model. In conclusion, overexpression of contributes to breast cancer metastasis through upregulation of . Targeting is a potential treatment for metastatic breast cancer as well as primary breast tumors with high expression. expression levels may be useful predictors of patient treatment and outcome responses.
在肿瘤发生和转移过程中,整合素调节重塑细胞外基质的蛋白水解酶的定位和活性。先前的研究表明,阻断αβ可有效抑制多种癌细胞类型的增殖、血管生成和存活。然而,关于整合素亚基α-V基因()在转移性乳腺癌中的功能作用知之甚少。在本研究中,使用基因敲低来确定促进肿瘤发生、转移、增殖、侵袭和细胞自我更新的分子机制。研究了整合素α-V拮抗剂西仑吉肽对乳腺癌治疗的有效性。对公开可用数据的分析表明,该基因的过表达与乳腺癌患者无复发生存期差有关。该基因的沉默通过改变和的表达来抑制乳腺癌细胞系的细胞增殖、侵袭和自我更新。在转移性乳腺癌动物模型中,使用西仑吉肽可显著减少肺转移。总之,该基因的过表达通过上调促进乳腺癌转移。靶向该基因是转移性乳腺癌以及高表达原发性乳腺癌的潜在治疗方法。该基因的表达水平可能是患者治疗和结果反应的有用预测指标。