RRC ID 72019
Author Liang C, Fukuda T, Isaji T, Duan C, Song W, Wang Y, Gu J.
Title α1,6-Fucosyltransferase contributes to cell migration and proliferation as well as to cancer stemness features in pancreatic carcinoma.
Journal Biochim Biophys Acta Gen Subj
Abstract BACKGROUND:Pancreatic carcinoma is one of the deadliest malignant diseases, in which the increased expression of α1,6-fucosyltransferase (FUT8), a sole enzyme responsible for catalyzing core fucosylation, has been reported. However, its pathological roles and regulatory mechanisms remain largely unknown. Here, we use two pancreatic adenocarcinoma cell lines, MIA PaCa-2 and PANC-1 cells, as cell models, to explore the relationship of FUT8 with the malignant transformation of PDAC.
METHODS:FUT8 knockout (FUT8-KO) cells were established by the CRISPR/Cas9 system. Cell migration was analyzed by transwell and wound-healing assays. Cell proliferation was examined by MTT and colony-formation assays. Cancer stemness markers and spheroid formations were used to analyzed cancer stemness features.
RESULTS:Deficiency of FUT8 inhibited cell migration and proliferation in both MIA PaCa-2 and PANC-1 cells compared with wild-type cells. Moreover, the expression levels of cancer stemness markers such as EpCAM, CXCR4, c-Met, and CD133 were decreased in the FUT8-KO cells compared with wild-type cells. Also, the spheroid formations in the KO cells were loose and unstable, which could be reversed by restoration with FUT8 gene in the KO cells. Additionally, FUT8-KO increased the chemosensitivity to gemcitabine, which is the first-line therapy for advanced pancreatic cancer.
CONCLUSIONS:FUT8-KO reduced the cell proliferation and migration. Our results are the first to suggest that the expression of FUT8 is involved in regulating the stemness features of pancreatic cancer cells.
GENERAL SIGNIFICANCE:FUT8 could provide novel insights for the treatment of pancreatic carcinoma.
Volume 1865(6)
Pages 129870
Published 2021-6-1
DOI 10.1016/j.bbagen.2021.129870
PII S0304-4165(21)00029-5
PMID 33571582
MeSH Adenocarcinoma / genetics Adenocarcinoma / metabolism Adenocarcinoma / pathology* Animals Apoptosis Biomarkers, Tumor / genetics Biomarkers, Tumor / metabolism* Cell Movement* Cell Proliferation Female Fucosyltransferases / genetics Fucosyltransferases / metabolism* Gene Expression Regulation, Neoplastic* Humans Mice Mice, Inbred BALB C Mice, Nude Neoplastic Stem Cells / metabolism Neoplastic Stem Cells / pathology* Pancreatic Neoplasms / genetics Pancreatic Neoplasms / metabolism Pancreatic Neoplasms / pathology* Tumor Cells, Cultured Xenograft Model Antitumor Assays
IF 3.422
Human and Animal Cells MIA Paca2(RCB2094) PANC-1(RCB2095)