Please use this identifier to cite or link to this item:
https://doi.org/10.18632/oncotarget.14563
DC Field | Value | |
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dc.title | A novel ZEB1/HAS2 positive feedback loop promotes EMT in breast cancer | |
dc.contributor.author | Preca, B.-T | |
dc.contributor.author | Bajdak, K | |
dc.contributor.author | Mock, K | |
dc.contributor.author | Lehmann, W | |
dc.contributor.author | Sundararajan, V | |
dc.contributor.author | Bronsert, P | |
dc.contributor.author | Matzge-Ogi, A | |
dc.contributor.author | Orian-Rousseau, V | |
dc.contributor.author | Brabletz, S | |
dc.contributor.author | Brabletz, T | |
dc.contributor.author | Maurer, J | |
dc.contributor.author | Stemmler, M.P | |
dc.date.accessioned | 2020-10-26T04:59:11Z | |
dc.date.available | 2020-10-26T04:59:11Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Preca, B.-T, Bajdak, K, Mock, K, Lehmann, W, Sundararajan, V, Bronsert, P, Matzge-Ogi, A, Orian-Rousseau, V, Brabletz, S, Brabletz, T, Maurer, J, Stemmler, M.P (2017). A novel ZEB1/HAS2 positive feedback loop promotes EMT in breast cancer. Oncotarget 8 (7) : 11530-11543. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.14563 | |
dc.identifier.issn | 19492553 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/179888 | |
dc.description.abstract | Cancer metastasis is the main reason for poor patient survival. Tumor cells delaminate from the primary tumor by induction of epithelial-mesenchymal transition (EMT). EMT is mediated by key transcription factors, including ZEB1, activated by tumor cell interactions with stromal cells and the extracellular matrix (ECM). ZEB1- mediated EMT and motility is accompanied by substantial cell reprogramming and the acquisition of a stemness phenotype. However, understanding of the underlying mechanism is still incomplete. We identified hyaluronic acid (HA), one major ECM proteoglycan and enriched in mammary tumors, to support EMT and enhance ZEB1 expression in cooperation with CD44s. In breast cancer cell lines HA is synthesized mainly by HAS2, which was already shown to be implicated in cancer progression. ZEB1 and HAS2 expression strongly correlates in various cancer entities and high HAS2 levels associate with an early relapse. We identified HAS2, tumor cell-derived HA and ZEB1 to form a positive feedback loop as ZEB1, elevated by HA, directly activates HAS2 expression. In an in vitro differentiation model HA-conditioned medium of breast cancer cells is enhancing osteoclast formation, an indicator of tumor cell-induced osteolysis that facilitates formation of bone metastasis. In combination with the previously identified ZEB1/ESRP1/CD44s feedback loop, we found a novel autocrine mechanism how ZEB1 is accelerating EMT. | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | Unpaywall 20201031 | |
dc.subject | epithelial splicing regulatory protein 1 | |
dc.subject | Hermes antigen | |
dc.subject | hyaluronic acid | |
dc.subject | hyaluronic acid synthase 2 | |
dc.subject | proteoglycan | |
dc.subject | regulator protein | |
dc.subject | synthetase | |
dc.subject | transcription factor ZEB1 | |
dc.subject | transforming growth factor beta | |
dc.subject | unclassified drug | |
dc.subject | glucuronosyltransferase | |
dc.subject | HAS2 protein, human | |
dc.subject | transcription factor ZEB1 | |
dc.subject | ZEB1 protein, human | |
dc.subject | Article | |
dc.subject | bone metastasis | |
dc.subject | breast cancer | |
dc.subject | breast cancer cell line | |
dc.subject | cancer growth | |
dc.subject | cancer prognosis | |
dc.subject | cancer recurrence | |
dc.subject | cell differentiation | |
dc.subject | controlled study | |
dc.subject | correlational study | |
dc.subject | epithelial mesenchymal transition | |
dc.subject | feedback system | |
dc.subject | gene | |
dc.subject | gene activation | |
dc.subject | gene expression | |
dc.subject | genetic association | |
dc.subject | HAS2 gene | |
dc.subject | human | |
dc.subject | human cell | |
dc.subject | human tissue | |
dc.subject | in vitro study | |
dc.subject | osteoclast | |
dc.subject | osteolysis | |
dc.subject | positive feedback loop | |
dc.subject | protein function | |
dc.subject | tumor growth | |
dc.subject | ZEB1 gene | |
dc.subject | breast tumor | |
dc.subject | chromatin immunoprecipitation | |
dc.subject | enzyme linked immunosorbent assay | |
dc.subject | epithelial mesenchymal transition | |
dc.subject | female | |
dc.subject | fluorescent antibody technique | |
dc.subject | gene expression regulation | |
dc.subject | immunohistochemistry | |
dc.subject | Kaplan Meier method | |
dc.subject | metabolism | |
dc.subject | pathology | |
dc.subject | physiological feedback | |
dc.subject | physiology | |
dc.subject | polymerase chain reaction | |
dc.subject | tumor cell line | |
dc.subject | tumor invasion | |
dc.subject | Western blotting | |
dc.subject | Blotting, Western | |
dc.subject | Breast Neoplasms | |
dc.subject | Cell Differentiation | |
dc.subject | Cell Line, Tumor | |
dc.subject | Chromatin Immunoprecipitation | |
dc.subject | Enzyme-Linked Immunosorbent Assay | |
dc.subject | Epithelial-Mesenchymal Transition | |
dc.subject | Feedback, Physiological | |
dc.subject | Female | |
dc.subject | Fluorescent Antibody Technique | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.subject | Glucuronosyltransferase | |
dc.subject | Humans | |
dc.subject | Immunohistochemistry | |
dc.subject | Kaplan-Meier Estimate | |
dc.subject | Neoplasm Invasiveness | |
dc.subject | Osteoclasts | |
dc.subject | Polymerase Chain Reaction | |
dc.subject | Zinc Finger E-box-Binding Homeobox 1 | |
dc.type | Article | |
dc.contributor.department | CANCER SCIENCE INSTITUTE OF SINGAPORE | |
dc.description.doi | 10.18632/oncotarget.14563 | |
dc.description.sourcetitle | Oncotarget | |
dc.description.volume | 8 | |
dc.description.issue | 7 | |
dc.description.page | 11530-11543 | |
Appears in Collections: | Staff Publications Elements |
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