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Article: DESC1, a novel tumor suppressor, sensitizes cells to apoptosis by downregulating the EGFR/AKT pathway in esophageal squamous cell carcinoma

TitleDESC1, a novel tumor suppressor, sensitizes cells to apoptosis by downregulating the EGFR/AKT pathway in esophageal squamous cell carcinoma
Authors
KeywordsDifferentially expressed in squamous cell carcinoma 1
Transmembrane serine protease
Esophageal squamous cell carcinoma
Apoptosis
Issue Date2016
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
Citation
International Journal of Cancer, 2016, v. 138 n. 12, p. 2940-2951 How to Cite?
AbstractEsophageal cancer is ranked as the eighth most common cancer and the sixth leading cause of cancer deaths worldwide. To identify candidate tumor suppressor genes related to esophageal squamous cell carcinoma (ESCC) development, a cDNA microarray analysis was performed using paired tumor and nontumor tissue samples from ESCC patients. Differentially expressed in squamous cell carcinoma 1 (DESC1), which belongs to the Type II transmembrane serine protease family, was frequently downregulated in ESCC. This study aims to elucidate the molecular mechanism for the tumor suppressive function of DESC1 in ESCC. We show that DESC1 reduced cell viability and sensitized cells to apoptosis, when cells were under apoptotic stimuli. The proapoptotic effect of DESC1 was mediated through downregulating AKT1 activation and the restoration of AKT activation by the introduction of the constitutively active AKT, myr‐AKT, abolished the apoptosis‐sensitizing effect of DESC1. DESC1 also reduced EGFR protein level, which was abrogated when the proteolytic function of DESC1 was lost, suggesting that DESC1 cleaved EGFR and downregulated the EGFR/AKT pathway to favor apoptosis. The transmembrane localization and the structural domains provide an opportunity for DESC1 to interact with the extracellular environment. The importance of such interaction was highlighted by the finding that DESC1 reduced cell colony formation ability in three‐dimensional culture. In line with this, DESC1 reduced tumor growth kinetics in the in vivo orthotopic tumorigenesis assay. Taken together, our novel findings suggest how DESC1 may suppress ESCC development by sensitizing cells to apoptosis under an apoptotic stimulus through downregulating the EGFR/AKT signaling pathway.
Persistent Identifierhttp://hdl.handle.net/10722/227215
ISSN
2023 Impact Factor: 5.7
2023 SCImago Journal Rankings: 2.131
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorNg, HY-
dc.contributor.authorKo, JMY-
dc.contributor.authorYu, VZ-
dc.contributor.authorIp, JCY-
dc.contributor.authorDai, W-
dc.contributor.authorCal, S-
dc.contributor.authorLung, ML-
dc.date.accessioned2016-07-18T09:09:08Z-
dc.date.available2016-07-18T09:09:08Z-
dc.date.issued2016-
dc.identifier.citationInternational Journal of Cancer, 2016, v. 138 n. 12, p. 2940-2951-
dc.identifier.issn0020-7136-
dc.identifier.urihttp://hdl.handle.net/10722/227215-
dc.description.abstractEsophageal cancer is ranked as the eighth most common cancer and the sixth leading cause of cancer deaths worldwide. To identify candidate tumor suppressor genes related to esophageal squamous cell carcinoma (ESCC) development, a cDNA microarray analysis was performed using paired tumor and nontumor tissue samples from ESCC patients. Differentially expressed in squamous cell carcinoma 1 (DESC1), which belongs to the Type II transmembrane serine protease family, was frequently downregulated in ESCC. This study aims to elucidate the molecular mechanism for the tumor suppressive function of DESC1 in ESCC. We show that DESC1 reduced cell viability and sensitized cells to apoptosis, when cells were under apoptotic stimuli. The proapoptotic effect of DESC1 was mediated through downregulating AKT1 activation and the restoration of AKT activation by the introduction of the constitutively active AKT, myr‐AKT, abolished the apoptosis‐sensitizing effect of DESC1. DESC1 also reduced EGFR protein level, which was abrogated when the proteolytic function of DESC1 was lost, suggesting that DESC1 cleaved EGFR and downregulated the EGFR/AKT pathway to favor apoptosis. The transmembrane localization and the structural domains provide an opportunity for DESC1 to interact with the extracellular environment. The importance of such interaction was highlighted by the finding that DESC1 reduced cell colony formation ability in three‐dimensional culture. In line with this, DESC1 reduced tumor growth kinetics in the in vivo orthotopic tumorigenesis assay. Taken together, our novel findings suggest how DESC1 may suppress ESCC development by sensitizing cells to apoptosis under an apoptotic stimulus through downregulating the EGFR/AKT signaling pathway.-
dc.languageeng-
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home-
dc.relation.ispartofInternational Journal of Cancer-
dc.subjectDifferentially expressed in squamous cell carcinoma 1-
dc.subjectTransmembrane serine protease-
dc.subjectEsophageal squamous cell carcinoma-
dc.subjectApoptosis-
dc.titleDESC1, a novel tumor suppressor, sensitizes cells to apoptosis by downregulating the EGFR/AKT pathway in esophageal squamous cell carcinoma-
dc.typeArticle-
dc.identifier.emailNg, HY: hyng0812@hku.hk-
dc.identifier.emailKo, JMY: joko@hku.hk-
dc.identifier.emailYu, VZ: zvyu@hku.hk-
dc.identifier.emailIp, JCY: josephip@hku.hk-
dc.identifier.emailDai, W: weidai2@hku.hk-
dc.identifier.emailLung, ML: mlilung@hku.hk-
dc.identifier.authorityKo, JMY=rp02011-
dc.identifier.authorityYu, VZ=rp02756-
dc.identifier.authorityDai, W=rp02146-
dc.identifier.authorityLung, ML=rp00300-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1002/ijc.30034-
dc.identifier.pmid26856390-
dc.identifier.scopuseid_2-s2.0-84959280172-
dc.identifier.hkuros259641-
dc.identifier.volume138-
dc.identifier.issue12-
dc.identifier.spage2940-
dc.identifier.epage2951-
dc.identifier.isiWOS:000374140600018-
dc.publisher.placeUnited States-
dc.identifier.issnl0020-7136-

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