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. 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. 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. LOXL1 may function as an important tumour suppressor in regulating tumour growth, invasion and metastasis via negative regulation of YAP activity.

中文翻译：

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LOXL1 通过抑制 YAP 的转录活性来调节结直肠癌的恶性进展。

LOX-like 1 (LOXL1) 是一种赖氨酰氧化酶，新出现的证据揭示了它对恶性癌症进展的影响。然而，其在结直肠癌（CRC）中的作用和潜在的分子机制尚未阐明。LOXL1在结直肠癌中的表达通过免疫组织化学、蛋白质印迹和实时PCR检测。在体外，进行集落形成、伤口愈合、迁移和侵袭试验以研究 LOXL1 对细胞增殖、迁移和侵袭的影响。在体内，转移模型和小鼠异种移植物用于评估致瘤性和转移能力。分子生物学实验被用来揭示 LOXL1 调节 Hippo 通路的潜在机制。与癌组织相比，LOXL1在正常结肠组织中高表达。体外，在 CRC 细胞系中沉默 LOXL1 可显着增强迁移、侵袭和集落形成，而 LOXL1 的过表达则产生相反的效果。体内实验结果表明 LOXL1 在 CRC 细胞系中的过表达显着抑制了转移进展和肿瘤生长。从机制上讲，LOXL1 通过与 MST1/2 相互作用并增加 MST1/2 的磷酸化来抑制 Yes 相关蛋白 (YAP) 的转录活性。LOXL1 可能是重要的肿瘤抑制因子，通过负调节 YAP 活性来调节肿瘤生长、侵袭和转移。体内实验结果表明 LOXL1 在 CRC 细胞系中的过表达显着抑制了转移进展和肿瘤生长。从机制上讲，LOXL1 通过与 MST1/2 相互作用并增加 MST1/2 的磷酸化来抑制 Yes 相关蛋白 (YAP) 的转录活性。LOXL1 可能是重要的肿瘤抑制因子，通过负调节 YAP 活性来调节肿瘤生长、侵袭和转移。体内实验结果表明 LOXL1 在 CRC 细胞系中的过表达显着抑制了转移进展和肿瘤生长。从机制上讲，LOXL1 通过与 MST1/2 相互作用并增加 MST1/2 的磷酸化来抑制 Yes 相关蛋白 (YAP) 的转录活性。LOXL1 可能是重要的肿瘤抑制因子，通过负调节 YAP 活性来调节肿瘤生长、侵袭和转移。