LOXL1 modulates the malignant progression of colorectal cancer by inhibiting the transcriptional activity of YAP
Autor: | Chao Wu, Yuhong Wang, E. Maruthi Prasad, Lin Hu, Yunliang Wang, Bo Mao, Jing Wang, Y. Eugene Chin, Linpeng Wu |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male Transcriptional Activation Colorectal cancer Mice Nude lcsh:Medicine Lysyl oxidase Apoptosis Biology medicine.disease_cause Yes-associated protein Biochemistry Metastasis 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Line Tumor medicine Gene silencing Animals Humans Neoplasm Invasiveness lcsh:QH573-671 Molecular Biology Adaptor Proteins Signal Transducing Hippo signaling pathway Mice Inbred BALB C Cell growth lcsh:Cytology Research lcsh:R Cancer YAP-Signaling Proteins Cell Biology medicine.disease eye diseases Gene Expression Regulation Neoplastic 030104 developmental biology LOXL1 030220 oncology & carcinogenesis Tumorigenesis Cancer research Disease Progression Amino Acid Oxidoreductases Carcinogenesis Colorectal Neoplasms Transcription Factors |
Zdroj: | Cell Communication and Signaling, Vol 18, Iss 1, Pp 1-16 (2020) Cell Communication and Signaling : CCS |
Popis: | 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. Graphical abstract |
Databáze: | OpenAIRE |
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