| http://purl.uniprot.org/citations/30374053 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30374053 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30374053 | http://www.w3.org/2000/01/rdf-schema#comment | "Vesicular acidification and trafficking are associated with various cellular processes. However, their pathologic relevance to cancer remains elusive. We identified transmembrane protein 9 (TMEM9) as a vesicular acidification regulator. TMEM9 is highly upregulated in colorectal cancer. Proteomic and biochemical analyses show that TMEM9 binds to and facilitates assembly of vacuolar-ATPase (v-ATPase), a vacuolar proton pump, resulting in enhanced vesicular acidification and trafficking. TMEM9-v-ATPase hyperactivates Wnt/β-catenin signalling via lysosomal degradation of adenomatous polyposis coli (APC). Moreover, TMEM9 transactivated by β-catenin functions as a positive feedback regulator of Wnt signalling in colorectal cancer. Genetic ablation of TMEM9 inhibits colorectal cancer cell proliferation in vitro, ex vivo and in vivo mouse models. Moreover, administration of v-ATPase inhibitors suppresses intestinal tumorigenesis of APC mouse models and human patient-derived xenografts. Our results reveal the unexpected roles of TMEM9-controlled vesicular acidification in hyperactivating Wnt/β-catenin signalling through APC degradation, and propose the blockade of TMEM9-v-ATPase as a viable option for colorectal cancer treatment."xsd:string |
| http://purl.uniprot.org/citations/30374053 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41556-018-0219-8"xsd:string |
| http://purl.uniprot.org/citations/30374053 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41556-018-0219-8"xsd:string |
| http://purl.uniprot.org/citations/30374053 | http://purl.uniprot.org/core/author | "Chen J."xsd:string |
| http://purl.uniprot.org/citations/30374053 | http://purl.uniprot.org/core/author | "Chen J."xsd:string |
| http://purl.uniprot.org/citations/30374053 | http://purl.uniprot.org/core/author | "Lee S."xsd:string |
| http://purl.uniprot.org/citations/30374053 | http://purl.uniprot.org/core/author | "Lee S."xsd:string |
| http://purl.uniprot.org/citations/30374053 | http://purl.uniprot.org/core/author | "Lee S.H."xsd:string |
| http://purl.uniprot.org/citations/30374053 | http://purl.uniprot.org/core/author | "Lee S.H."xsd:string |
| http://purl.uniprot.org/citations/30374053 | http://purl.uniprot.org/core/author | "Kim M.J."xsd:string |
| http://purl.uniprot.org/citations/30374053 | http://purl.uniprot.org/core/author | "Kim M.J."xsd:string |
| http://purl.uniprot.org/citations/30374053 | http://purl.uniprot.org/core/author | "Zhang J."xsd:string |
| http://purl.uniprot.org/citations/30374053 | http://purl.uniprot.org/core/author | "Zhang J."xsd:string |
| http://purl.uniprot.org/citations/30374053 | http://purl.uniprot.org/core/author | "Wang W."xsd:string |
| http://purl.uniprot.org/citations/30374053 | http://purl.uniprot.org/core/author | "Wang W."xsd:string |
| http://purl.uniprot.org/citations/30374053 | http://purl.uniprot.org/core/author | "Ji H."xsd:string |
| http://purl.uniprot.org/citations/30374053 | http://purl.uniprot.org/core/author | "Ji H."xsd:string |
| http://purl.uniprot.org/citations/30374053 | http://purl.uniprot.org/core/author | "Jung H.Y."xsd:string |
| http://purl.uniprot.org/citations/30374053 | http://purl.uniprot.org/core/author | "Jung H.Y."xsd:string |
| http://purl.uniprot.org/citations/30374053 | http://purl.uniprot.org/core/author | "Wu J.Y."xsd:string |
| http://purl.uniprot.org/citations/30374053 | http://purl.uniprot.org/core/author | "Wu J.Y."xsd:string |
| http://purl.uniprot.org/citations/30374053 | http://purl.uniprot.org/core/author | "Park J.I."xsd:string |
| http://purl.uniprot.org/citations/30374053 | http://purl.uniprot.org/core/author | "Park J.I."xsd:string |