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
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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