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Intramembrane proteolysis of an extracellular serine protease, epithin/PRSS14, enables its intracellular nuclear function

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dc.contributor.author김상범-
dc.date.accessioned2020-09-28T12:01:37Z-
dc.date.available2020-09-28T12:01:37Z-
dc.date.issued2020-06-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/179319-
dc.description.abstractBackground: Epithin/PRSS14, a type II transmembrane serine protease, is an emerging target of cancer therapy because of its critical roles in tumor progression and metastasis. In many circumstances, the protease, through its ectodomain shedding, exists as a soluble form and performs its proteolytic functions in extracellular environments increasing cellular invasiveness. The seemingly functional integrity of the soluble form raises the question of why the protease is initially made as a membrane-associated protein. Results: In this report, we show that the epithin/PRSS14 intracellular domain (EICD) can be released from the membrane by the action of signal peptide peptidase-like 2b (SPPL2b) after ectodomain shedding. The EICD preferentially localizes in the nucleus and can enhance migration, invasion, and metastasis of epithelial cancer when heterologously expressed. Unbiased RNA-seq analysis and subsequent antibody arrays showed that EICD could control the gene expression of chemokines involved in cell motility, by increasing their promoter activities. Finally, bioinformatics analysis provided evidence for the clinical significance of the intramembrane proteolysis of epithin/PRSS14 by revealing that the poor survival of estrogen receptor (ER)-negative breast cancer patients with high epithin/PRSS14 expression is further worsened by high levels of SPPL2b. Conclusions: These results show that ectodomain shedding of epithin/PRSS14 can initiate a unique and synchronized bidirectional signal for cancer metastasis: extracellularly broadening proteolytic modification of the surrounding environment and intracellularly reprogramming the transcriptome for metastatic conversion. Clinically, this study also suggests that the intracellular function of epithin/PRSS14 should be considered for targeting this protease for anti-cancer treatment.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherBioMed Central-
dc.relation.isPartOfBMC BIOLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.titleIntramembrane proteolysis of an extracellular serine protease, epithin/PRSS14, enables its intracellular nuclear function-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentBioMedical Science Institute (의생명과학부)-
dc.contributor.googleauthorYoungkyung Cho-
dc.contributor.googleauthorSang Bum Kim-
dc.contributor.googleauthorJiyoon Kim-
dc.contributor.googleauthorAn Vuong Quynh Pham-
dc.contributor.googleauthorMin Ji Yoon-
dc.contributor.googleauthorJeong Hwan Park-
dc.contributor.googleauthorKi-Tae Hwang-
dc.contributor.googleauthorDongeun Park-
dc.contributor.googleauthorYongcheol Cho-
dc.contributor.googleauthorMoon Gyo Kim-
dc.contributor.googleauthorChungho Kim-
dc.identifier.doi10.1186/s12915-020-00787-3-
dc.contributor.localIdA05691-
dc.relation.journalcodeJ03865-
dc.identifier.eissn1741-7007-
dc.identifier.pmid32493324-
dc.subject.keywordEpithin/PRSS14-
dc.subject.keywordMetastasis-
dc.subject.keywordRegulated intramembrane proteolysis-
dc.subject.keywordTranscriptional regulation-
dc.contributor.alternativeNameKim, Sang Bum-
dc.contributor.affiliatedAuthor김상범-
dc.citation.volume18-
dc.citation.number1-
dc.citation.startPage60-
dc.identifier.bibliographicCitationBMC BIOLOGY, Vol.18(1) : 60, 2020-06-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers

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