LOXL1 modulates the malignant progression of colorectal cancer by inhibiting the transcriptional activity of YAP
- PDF / 7,692,724 Bytes
- 16 Pages / 595.276 x 790.866 pts Page_size
- 89 Downloads / 158 Views
(2020) 18:148
RESEARCH
Open Access
LOXL1 modulates the malignant progression of colorectal cancer by inhibiting the transcriptional activity of YAP Lin Hu1†, Jing Wang1†, Yunliang Wang2†, Linpeng Wu1, Chao Wu1, Bo Mao3, E. Maruthi Prasad4, Yuhong Wang5* and Y. Eugene Chin1*
Abstract 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. Keywords: Colorectal cancer, LOXL1, Tumorigenesis, Yes-associated protein
Background Colorectal cancer (CRC) is ranked as the third most frequently diagnosed cancer and the second leading cause of cancer-related death worldwide [1]. Moreover, the fiveyear relative survival rate for surgical patients in the late stages of colon cancer is only approximately 10% [2], and * Correspondence: [email protected]; [email protected] † Lin Hu, Jing Wang and Yunliang Wang are co-first author 5 Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, China 1 Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China Full list of author information is available at the end of the article
over 50% of patients with colon cancer are clinically diagnosed at the late stages [3]. Invasion and distant metastasis of the tumours are considered to be the reasons leading most frequently to the mortalities associated with CRC. However, the mechanisms underlying this malignant progression are not fully understood. Therefore, investigation of the associated mechanisms is very important for developing strategies to treat patients with CRC. The Hippo pathway is an evolutionarily conserved tumour suppressor pathway be
Data Loading...
