Calotropin activates YAP through downregulation of LATS1 in colorectal cancer cells
Year: 2019
Type: article
Abstract: Limin Zhou,1,2,* Luliang Cai,3,* Yanzi Guo,4 Huanyu Zhang,1 Peng Wang,1 Guohui Yi,1,2 Yonghao Huang1,5 1Key Laboratory of Tropical Diseases and Translational Medicine of the Ministry of Education & Hainan Provincial Key Laboratory of Tropical Medicine, Hainan Medical College, Haikou 571199, People’s Republic of China; 2Public Research Laboratory, Hainan Medical College, Haikou 571199, People’s Republic of China; 3Department of Pediatrics, Hainan Provincial People’s Hospital, Haikou 570311, People’s Republic of China; 4Key Laboratory of Preclinical Pharmacology and Toxicology of Hainan Province, Hainan Medical College, Haikou 571199, People’s Republic of China; 5Department of Anesthesiology, Second Affiliated Hospital, Hainan Medical College, Haikou 571199, People’s Republic of China *These authors contributed equally to this work Objectives: Calotropin (CTP), a natural product isolated from Calotropis gigantea, has been identified as a potential anticancer agent. In this study, we aimed to investigate the effect CTP on colorectal cancer and the role of Yes-associated protein (YAP) in CTP-inhibited cell proliferation.Methods: Cell viability and cell proliferation were detected by MTT and BrdU assay. Western blotting and immunofluorescence were performed to determine CTP-induced YAP dephosphorylation and nuclear localization. Western blotting, siRNA transfection and RT-PCR analysis were carried out to investigate the mechanisms of CTP-mediated YAP activation. The anti-tumor activities of CTP were observed in mice tumor models.Results: We demonstrated that CTP inhibits the proliferation of colorectal cancer cells both in vitro and in vivo. Moreover, we showed that CTP activates YAP in colorectal cancer cells. Mechanistically, CTP promotes LATS1 degradation via the ubiquitination/proteasome pathway, resulting in YAP dephosphorylation and nuclear localization, leading to induce YAP target genes expression in colorectal cancer cells. Inhibition of YAP activity enhances CTP-mediated inhibition of cell proliferation, suggesting that YAP plays a protective role in CTP-induced antiproliferative effect.Conclusion: Our results demonstrate that CTP markedly inhibits tumor growth and activates a protective role of YAP in colorectal cancer cells, indicating that combination of CTP and YAP targeting drugs may be a promising strategy for colorectal cancer treatment.Keywords: colorectal cancer, calotropin, CTP, cell proliferation, YAP, LATS1
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4286784396