TMPRSS4 promotes cancer stem-like properties in prostate cancer cells through upregulation of SOX2 by SLUG and TWIST1

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dc.contributor.authorYunhee Lee-
dc.contributor.authorJunghwa Yoon-
dc.contributor.authorDongjoon Ko-
dc.contributor.authorMinyeong Yu-
dc.contributor.authorS Lee-
dc.contributor.authorSemi Kim-
dc.date.accessioned2021-11-24T15:30:19Z-
dc.date.available2021-11-24T15:30:19Z-
dc.date.issued2021-
dc.identifier.issn1756-9966-
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/25048-
dc.description.abstractBackground: Transmembrane serine protease 4 (TMPRSS4) is a cell surface-anchored serine protease. Elevated expression of TMPRSS4 correlates with poor prognosis in colorectal cancer, gastric cancer, prostate cancer, non-small cell lung cancer, and other cancers. Previously, we demonstrated that TMPRSS4 promotes invasion and proliferation of prostate cancer cells. Here, we investigated whether TMPRSS4 confers cancer stem-like properties to prostate cancer cells and characterized the underlying mechanisms. Methods: Acquisition of cancer stem-like properties by TMPRSS4 was examined by monitoring anchorage-independent growth, tumorsphere formation, aldehyde dehydrogenase (ALDH) activation, and resistance to anoikis and drugs in vitro and in an early metastasis model in vivo. The underlying molecular mechanisms were evaluated, focusing on stemness-related factors regulated by epithelial-mesenchymal transition (EMT)-inducing transcription factors. Clinical expression and significance of TMPRSS4 and stemness-associated factors were explored by analyzing datasets from The Cancer Genome Atlas (TCGA). Results: TMPRSS4 promoted anchorage-independent growth, ALDH activation, tumorsphere formation, and therapeutic resistance of prostate cancer cells. In addition, TMPRSS4 promoted resistance to anoikis, thereby increasing survival of circulating tumor cells and promoting early metastasis. These features were accompanied by upregulation of stemness-related factors such as SOX2, BMI1, and CD133. SLUG and TWIST1, master EMT-inducing transcription factors, made essential contributions to TMPRSS4-mediated cancer stem cell (CSC) features through upregulation of SOX2. SLUG stabilized SOX2 via preventing proteasomal degradation through its interaction with SOX2, while TWIST1 upregulated transcription of SOX2 by interacting with the proximal E-box element in the SOX2 promoter. Clinical data showed that TMPRSS4 expression correlated with the levels of SOX2, PROM1, SNAI2, and TWIST1. Expression of SOX2 was positively correlated with that of TWIST1, but not with other EMT-inducing transcription factors, in various cancer cell lines. Conclusions: Together, these findings suggest that TMPRSS4 promotes CSC features in prostate cancer through upregulation of the SLUG- and TWIST1-induced stem cell factor SOX2 beyond EMT. Thus, TMPRSS4/SLUG-TWIST1/SOX2 axis may represent a novel mechanism involved in the control of tumor progression.-
dc.publisherSpringer-BMC-
dc.titleTMPRSS4 promotes cancer stem-like properties in prostate cancer cells through upregulation of SOX2 by SLUG and TWIST1-
dc.title.alternativeTMPRSS4 promotes cancer stem-like properties in prostate cancer cells through upregulation of SOX2 by SLUG and TWIST1-
dc.typeArticle-
dc.citation.titleJournal of Experimental & Clinical Cancer Research-
dc.citation.number0-
dc.citation.endPage372-
dc.citation.startPage372-
dc.citation.volume40-
dc.contributor.affiliatedAuthorYunhee Lee-
dc.contributor.affiliatedAuthorJunghwa Yoon-
dc.contributor.affiliatedAuthorDongjoon Ko-
dc.contributor.affiliatedAuthorMinyeong Yu-
dc.contributor.affiliatedAuthorSemi Kim-
dc.contributor.alternativeName이윤희-
dc.contributor.alternativeName윤정화-
dc.contributor.alternativeName고동준-
dc.contributor.alternativeName유민영-
dc.contributor.alternativeName이수진-
dc.contributor.alternativeName김세미-
dc.identifier.bibliographicCitationJournal of Experimental & Clinical Cancer Research, vol. 40, pp. 372-372-
dc.identifier.doi10.1186/s13046-021-02147-7-
dc.subject.keywordTMPRSS4-
dc.subject.keywordStemness-
dc.subject.keywordSOX2-
dc.subject.keywordSLUG-
dc.subject.keywordTWIST1-
dc.subject.localTMPRSS4-
dc.subject.localStemness-
dc.subject.localSOX2-
dc.subject.localSLUG-
dc.subject.localTWIST1-
dc.description.journalClassY-
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Division of Biomedical Research > Microbiome Convergence Research Center > 1. Journal Articles
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