Dataset Information

LKB1 and YAP phosphorylation play important roles in Celastrol-induced ?-catenin degradation in colorectal cancer.

ABSTRACT: Wnt/?-catenin and Hippo pathways play essential roles in the tumorigenesis and development of colorectal cancer. We found that Celastrol, isolated from Tripterygium wilfordii plant, exerted a significant inhibitory effect on colorectal cancer cell growth in vitro and in vivo, and further unraveled the molecular mechanisms. Celastrol induced ?-catenin degradation through phosphorylation of Yes-associated protein (YAP), a major downstream effector of Hippo pathway, and also Celastrol-induced ?-catenin degradation was dependent on liver kinase B1 (LKB1). Celastrol increased the transcriptional activation of LKB1, partially through the heat shock factor 1 (HSF1). Moreover, LKB1 activated AMP-activated protein kinase ? (AMPK?) and further phosphorylated YAP, which eventually promoted the degradation of ?-catenin. In addition, LKB1 deficiency promoted colorectal cancer cell growth and attenuated the inhibitory effect of Celastrol on colorectal cancer growth both in vitro and in vivo. Taken together, Celastrol inhibited colorectal cancer cell growth by promoting ?-catenin degradation via the HSF1-LKB1-AMPK?-YAP pathway. These results suggested that Celastrol may potentially serve as a future drug for colorectal cancer treatment.

SUBMITTER: Wang S

PROVIDER: S-EPMC6477772 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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LKB1 and YAP phosphorylation play important roles in Celastrol-induced β-catenin degradation in colorectal cancer.

Wang Shuren S Ma Kai K Zhou Cuiqi C Wang Yu Y Hu Guanghui G Chen Lechuang L Li Zhuo Z Hu Chenfei C Xu Qing Q Zhu Hongxia H Liu Mei M Xu Ningzhi N

Therapeutic advances in medical oncology 20190422

Wnt/β-catenin and Hippo pathways play essential roles in the tumorigenesis and development of colorectal cancer. We found that Celastrol, isolated from Tripterygium wilfordii plant, exerted a significant inhibitory effect on colorectal cancer cell growth in vitro and in vivo, and further unraveled the molecular mechanisms. Celastrol induced β-catenin degradation through phosphorylation of Yes-associated protein (YAP), a major downstream effector of Hippo pathway, and also Ce ...[more]

PMID: 31040884

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Dataset Information

LKB1 and YAP phosphorylation play important roles in Celastrol-induced ?-catenin degradation in colorectal cancer.

Publications

LKB1 and YAP phosphorylation play important roles in Celastrol-induced β-catenin degradation in colorectal cancer.

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