LOXL1 modulates the malignant progression of colorectal cancer by inhibiting the transcriptional activity of YAP
LOXL1 modulates the malignant progression of colorectal cancer by inhibiting the transcriptional activity of YAP
复制标题
LOXL1通过抑制YAP转录活性调节结直肠癌的恶性进展
DOI：
10.1186/s12964-020-00639-1
复制
发表时间：
2020-09-10
影响因子：
8.4
通讯作者：
Chin, Y. Eugene
中科院分区：
文献类型：
--
作者：
Hu, Lin;Wang, Jing;Chin, Y. Eugene
背景：LOX样1（LOXL 1）是一种赖氨酰氧化酶，新的证据显示其在恶性肿瘤进展中的作用。方法：采用免疫组化、Western blotting和real-time PCR方法检测LOXL 1在大肠癌中的表达。在体外，进行集落形成、伤口愈合、迁移和侵袭测定以研究LOXL 1对细胞增殖、迁移和侵袭的影响。在体内，使用转移模型和小鼠异种移植物来评估致瘤性和转移能力。结果：LOXL 1在正常结肠组织中的表达明显高于癌组织。在体外，在CRC细胞系中沉默LOXL 1显著增强迁移、侵袭和集落形成，而LOXL 1的过表达产生相反的效果。体内实验的结果表明，CRC细胞系中LOXL 1的过表达显著抑制了转移进展和肿瘤生长。LOXL 1通过与MST 1/2相互作用，增加MST 1/2的磷酸化水平，抑制雅普的转录活性。结论：LOXL 1可能通过负调控雅普的活性，在肿瘤的生长、侵袭和转移中发挥重要的抑癌作用。
Background: LOX-like 1 (LOXL1) is a lysyl oxidase, and emerging evidence has revealed its effect on malignant cancer progression. However, its role in colorectal cancer (CRC) and the underlying molecular mechanisms have not yet been elucidated.Methods: LOXL1 expression in colorectal cancer was detected by immunohistochemistry, western blotting and real-time PCR. In vitro, colony formation, wound healing, migration and invasion assays were performed to investigate the effects of LOXL1 on cell proliferation, migration and invasion. In vivo, metastasis models and mouse xenografts were used to assess tumorigenicity and metastasis ability. Molecular biology experiments were utilized to reveal the underlying mechanisms by which LOXL1 modulates the Hippo pathway.Results: LOXL1 was highly expressed in normal colon tissues compared with cancer tissues. In vitro,silencing LOXL1 in CRC cell lines dramatically enhanced migration, invasion, and colony formation, while overexpression of LOXL1 exerted the opposite effects. The results of the in vivo experiments demonstrated that the overexpression of LOXL1 in CRC cell lines drastically inhibited metastatic progression and tumour growth. Mechanistically, LOXL1 inhibited the transcriptional activity of Yes-associated protein (YAP) by interacting with MST1/2 and increasing the phosphorylation of MST1/2.Conclusions: LOXL1 may function as an important tumour suppressor in regulating tumour growth, invasion and metastasis via negative regulation of YAP activity.