File Download
  Links for fulltext
     (May Require Subscription)

Article: DEPDC1B Promotes Melanoma Angiogenesis and Metastasis through Sequestration of Ubiquitin Ligase CDC16 to Stabilize Secreted SCUBE3

TitleDEPDC1B Promotes Melanoma Angiogenesis and Metastasis through Sequestration of Ubiquitin Ligase CDC16 to Stabilize Secreted SCUBE3
Authors
KeywordsAngiogenesis
CDC16
DEPDC1B
Melanoma
SCUBE3
Issue Date2022
PublisherWiley Open Access. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2198-3844
Citation
Advanced Science, 2022, article no. 2105226 How to Cite?
AbstractThe ability of melanoma to acquire metastasis through the induction of angiogenesis is one of the major causes of skin cancer death. Here, it is found that high transcript levels of DEP domain containing 1B (DEPDC1B) in cutaneous melanomas are significantly associated with a poor prognosis. Tissue microarray analysis indicates that DEPDC1B expression is positively correlated with SOX10 in the different stages of melanoma. Consistently, DEPDC1B is both required and sufficient for melanoma growth, metastasis, angiogenesis, and functions as a direct downstream target of SOX10 to partly mediate its oncogenic activity. In contrast to other tumor types, the DEPDC1B-mediated enhancement of melanoma metastatic potential is not dependent on the activities of RHO GTPase signaling and canonical Wnt signaling, but is acquired through secretion of signal peptide, CUB domain and EGF like domain containing 3 (SCUBE3), which is crucial for promoting angiogenesis in vitro and in vivo. Mechanistically, DEPDC1B regulates SCUBE3 protein stability through the competitive association with ubiquitin ligase cell division cycle 16 (CDC16) to prevent SCUBE3 from undergoing degradation via the ubiquitin-proteasome pathway. Importantly, expression of SOX10, DEPDC1B, and SCUBE3 are positively correlated with microvessel density in the advanced stage of melanomas. In conclusion, it is revealed that a SOX10-DEPDC1B-SCUBE3 regulatory axis promotes melanoma angiogenesis and metastasis, which suggests that targeting secreted SCUBE3 can be a therapeutic strategy against metastatic melanoma.
Persistent Identifierhttp://hdl.handle.net/10722/310501
ISSN
2023 Impact Factor: 14.3
2023 SCImago Journal Rankings: 3.914
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHu, F-
dc.contributor.authorFong, KO-
dc.contributor.authorCheung, MPL-
dc.contributor.authorLiu, JA-
dc.contributor.authorLiang, R-
dc.contributor.authorLi, TW-
dc.contributor.authorSharma, R-
dc.contributor.authorIp, PPC-
dc.contributor.authorYang, X-
dc.contributor.authorCheung, M-
dc.date.accessioned2022-02-07T07:57:35Z-
dc.date.available2022-02-07T07:57:35Z-
dc.date.issued2022-
dc.identifier.citationAdvanced Science, 2022, article no. 2105226-
dc.identifier.issn2198-3844-
dc.identifier.urihttp://hdl.handle.net/10722/310501-
dc.description.abstractThe ability of melanoma to acquire metastasis through the induction of angiogenesis is one of the major causes of skin cancer death. Here, it is found that high transcript levels of DEP domain containing 1B (DEPDC1B) in cutaneous melanomas are significantly associated with a poor prognosis. Tissue microarray analysis indicates that DEPDC1B expression is positively correlated with SOX10 in the different stages of melanoma. Consistently, DEPDC1B is both required and sufficient for melanoma growth, metastasis, angiogenesis, and functions as a direct downstream target of SOX10 to partly mediate its oncogenic activity. In contrast to other tumor types, the DEPDC1B-mediated enhancement of melanoma metastatic potential is not dependent on the activities of RHO GTPase signaling and canonical Wnt signaling, but is acquired through secretion of signal peptide, CUB domain and EGF like domain containing 3 (SCUBE3), which is crucial for promoting angiogenesis in vitro and in vivo. Mechanistically, DEPDC1B regulates SCUBE3 protein stability through the competitive association with ubiquitin ligase cell division cycle 16 (CDC16) to prevent SCUBE3 from undergoing degradation via the ubiquitin-proteasome pathway. Importantly, expression of SOX10, DEPDC1B, and SCUBE3 are positively correlated with microvessel density in the advanced stage of melanomas. In conclusion, it is revealed that a SOX10-DEPDC1B-SCUBE3 regulatory axis promotes melanoma angiogenesis and metastasis, which suggests that targeting secreted SCUBE3 can be a therapeutic strategy against metastatic melanoma.-
dc.languageeng-
dc.publisherWiley Open Access. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2198-3844-
dc.relation.ispartofAdvanced Science-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectAngiogenesis-
dc.subjectCDC16-
dc.subjectDEPDC1B-
dc.subjectMelanoma-
dc.subjectSCUBE3-
dc.titleDEPDC1B Promotes Melanoma Angiogenesis and Metastasis through Sequestration of Ubiquitin Ligase CDC16 to Stabilize Secreted SCUBE3-
dc.typeArticle-
dc.identifier.emailCheung, MPL: mplcheun@hku.hk-
dc.identifier.emailSharma, R: rasharma@hku.hk-
dc.identifier.emailIp, PPC: philipip@hku.hk-
dc.identifier.emailCheung, M: mcheung9@hku.hk-
dc.identifier.authorityIp, PPC=rp01890-
dc.identifier.authorityCheung, M=rp00245-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1002/advs.202105226-
dc.identifier.pmid35088579-
dc.identifier.scopuseid_2-s2.0-85123755767-
dc.identifier.hkuros331710-
dc.identifier.spagearticle no. 2105226-
dc.identifier.epagearticle no. 2105226-
dc.identifier.isiWOS:000747680000001-
dc.publisher.placeGermany-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats