期刊
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
卷 39, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13046-020-1521-4
关键词
Musashi2; EGF; ZEB1; ERK; MAPK pathway; C-Myc; Epithelial mesenchymal transition; Pancreatic cancer
类别
资金
- Chinese National Science Foundation [81672835]
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, beta-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.
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