ReferenceID 5659
Correction of the tumor suppressor Salvador homolog-1 deficiency in tumors by lycorine as a new strategy in lung cancer therapy
Cell Death Dis
Salvador homolog-1 (SAV1) is a tumor suppressor required for activation of the tumor-suppressive Hippo pathway and inhibition of tumorigenesis. SAV1 is defective in several cancer types. SAV1 deficiency in cells promotes
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Record Fields
Scalar fields from the final reference record.
- Reference Id
- 5659
- Evidence Id
- 22249
- Core Evidence Id
- 22249
- Source Reference Id
- 4545
- Herb2 Reference Id
- HBREF005342
- Subject Paper Key
- HBIN034010_32439835
- Pubmed Id
- 32439835
- Doi
- 10.1038/s41419-020-2591-0
- Paper Title
- Correction of the tumor suppressor Salvador homolog-1 deficiency in tumors by lycorine as a new strategy in lung cancer therapy
- Paper Abstract
- Salvador homolog-1 (SAV1) is a tumor suppressor required for activation of the tumor-suppressive Hippo pathway and inhibition of tumorigenesis. SAV1 is defective in several cancer types. SAV1 deficiency in cells promotes tumorigenesis and cancer metastasis, and is closely associated with poor prognosis for cancer patients. However, investigation of therapeutic strategies to target SAV1 deficiency in cancer is lacking. Here we found that the small molecule lycorine notably increased SAV1 levels in lung cancer cells by inhibiting SAV1 degradation via a ubiquitin-lysosome system, and inducing phosphorylation and activation of the SAV1-interacting protein mammalian Ste20-like 1 (MST1). MST1 activation then caused phosphorylation, ubiquitination, and degradation of the oncogenic Yes-associated protein (YAP), therefore inhibiting YAP-activated transcription of oncogenic genes and tumorigenic AKT and NF-kappaB signal pathways. Strikingly, treating tumor-bearing xenograft mice with lycorine increased SAV1 levels, and strongly inhibited tumor growth, vasculogenic mimicry, and metastasis. This work indicates that correcting SAV1 deficiency in lung cancer cells is a new strategy for cancer therapy. Our findings provide a new platform for developing novel cancer therapeutics.
- Journal
- Cell Death Dis
- Publish Year
- 2020
- Experiment Subject
- mouse; patient
- Experiment Type
- Animal Experiment
- Phenotype Related
- Sav1 Deficiency; Tumor; Cancer; Lung Cancer
- Paper Title Cn
- Paper Title En
- Correction of the tumor suppressor Salvador homolog-1 deficiency in tumors by lycorine as a new strategy in lung cancer therapy
- Bilingual Status
- semi_complete