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Musashi2 promotes EGF-induced EMT in pancreatic cancer via ZEB1-ERK/MAPK signaling.
- Source :
-
Journal of Experimental & Clinical Cancer Research (17569966) . 1/17/2020, Vol. 39 Issue 1, p1-14. 14p. - Publication Year :
- 2020
-
Abstract
- Background: Our previous study showed Musashi2 (MSI2) promoted chemotherapy resistance and pernicious biology of pancreatic cancer (PC) by down-regulating Numb and p53. We further explored the novel molecular mechanism involving its oncogenic role in PC development. Methods: We investigated the potential role and mechanism of MSI2 in EGF-induced EMT in PC in vitro and vivo. Results: EGF enhanced EGFR (epidermal growth factor receptor) phosphorylation, induced EMT and activated ZEB1-ERK/MAPK signaling in 2 PC cells. However, MSI2 silencing reversed EGF stimulated function, including inhibiting EGF-promoted EMT-like cell morphology and EGF-enhanced cell invasion and migration. Meanwhile, MSI2 silencing inhibited EGF-enhanced EGFR phosphorylation at tyrosine 1068 and reversed EGF-induced change of the key proteins in EMT and ZEB1-ERK/MAPK signaling (ZEB1, E-cad, ZO-1, β-catenin, pERK and c-Myc). Additionally, MSI2 was co-stained and co-immunoprecipitated with ZEB1, pERK and c-Myc in PC cells by IF and co-IP, implying a close interaction between them. In vivo, MSI2 silencing inhibited pancreatic tumor size in situ and distant liver metastases. A close relationship of MSI2 with EMT and ZEB1-ERK/MAPK signaling were also observed in vivo and human PC samples, which coordinately promoted the poor prognosis of PC patients. Conclusions: MSI2 promotes EGF-induced EMT in PC via ZEB1-ERK/MAPK signaling. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17569966
- Volume :
- 39
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Experimental & Clinical Cancer Research (17569966)
- Publication Type :
- Academic Journal
- Accession number :
- 141284744
- Full Text :
- https://doi.org/10.1186/s13046-020-1521-4