RRC ID 63659
著者 Chen R, Masuo K, Yogo A, Yokoyama S, Sugiyama A, Seno H, Yoshizawa A, Takaishi S.
タイトル SNAIL regulates gastric carcinogenesis through CCN3 and NEFL.
ジャーナル Carcinogenesis
Abstract Among cancer cells, there are specific cell populations of whose activities are comparable to those of stem cells in normal tissues, and for whom the levels of cell dedifferentiation are reported to correlate with poor prognosis. Information concerning the mechanisms that modulate the stemness like traits of cancer cells is limited. Therefore, we examined five gastric cancer cell lines and isolated gastric oncospheres from three gastric cancer cell lines. The gastric cancer cells that expanded in the spheres expressed relatively elevated proportion of CD44, which is a marker of gastric cancer stem cells (CSCs), and displayed many properties of CSCs, for example: chemoresistance, tumorigenicity and epithelial-mesenchymal transition (EMT) acquisition. SNAIL, which is a key factor in EMT, was highly expressed in the gastric spheres. Microarray analysis in gastric cancer cell line HGC27 showed that CCN3 and NEFL displayed the greatest differential expression by knocking down of SNAIL; the former was upregulated and the latter downregulated, respectively. Downregulation of CCN3 and upregulation of NEFL gene expression impaired the SNAIL-dependent EMT activity: high tumorigenicity, and chemoresistance in gastric cancer cells. Thus, approach that disrupts SNAIL/CCN3/NEFL axis may be credible in inhibiting gastric cancer development.
巻・号 42(2)
ページ 190-201
公開日 2021-2-25
DOI 10.1093/carcin/bgaa133
PII 6031453
PMID 33313663
MeSH Animals Carcinogenesis / genetics* Cell Line, Tumor Cell Proliferation Down-Regulation Drug Resistance, Neoplasm / genetics Epithelial-Mesenchymal Transition / genetics Fluorouracil / pharmacology Fluorouracil / therapeutic use Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Humans Mice Neoplastic Stem Cells / pathology Nephroblastoma Overexpressed Protein / genetics* Nephroblastoma Overexpressed Protein / metabolism Neurofilament Proteins / genetics* Neurofilament Proteins / metabolism Signal Transduction / genetics Snail Family Transcription Factors / genetics Snail Family Transcription Factors / metabolism* Stomach / pathology Stomach Neoplasms / drug therapy Stomach Neoplasms / genetics* Stomach Neoplasms / pathology Up-Regulation Xenograft Model Antitumor Assays
IF 4.603
リソース情報
ヒト・動物細胞 HGC-27(RCB0500)