RRC ID 69513
Author Masuo K, Chen R, Yogo A, Sugiyama A, Fukuda A, Masui T, Uemoto S, Seno H, Takaishi S.
Title SNAIL2 contributes to tumorigenicity and chemotherapy resistance in pancreatic cancer by regulating IGFBP2.
Journal Cancer Sci
Abstract Pancreatic cancer has an extremely poor prognosis because of its resistance to conventional therapies. Cancer stem cell (CSC)-targeted therapy is considered a promising approach for this disease. Epithelial-mesenchymal transition-inducing transcription factors (EMT-TFs) contribute to CSC properties in some solid tumors; however, this mechanism has not been fully elucidated in pancreatic cancer. Zinc finger protein, SNAIL2 (also known as SLUG), is a member of the SNAIL superfamily of EMT-TFs and is commonly overexpressed in pancreatic cancer. Patients exhibiting high SNAIL2 expression have a poor prognosis. In this study, we showed that the suppression of SNAIL2 expression using RNA interference decreased tumorigenicity in vitro (sphere formation assay) and in vivo (xenograft assay) in 2 pancreatic cancer cell lines, KLM1 and KMP5. In addition, SNAIL2 suppression resulted in increased sensitivity to gemcitabine and reduced the expression of CD44, a pancreatic CSC marker. Moreover, experiments on tumor spheroids established from surgically resected pancreatic cancer tissues yielded similar results. A microarray analysis revealed that the mechanism was mediated by insulin-like growth factor (IGF) binding protein 2. These results indicate that IGFBP2 regulated by SNAIL2 may represent an effective therapeutic target for pancreatic cancer.
Volume 112(12)
Pages 4987-4999
Published 2021-12-1
DOI 10.1111/cas.15162
PMID 34628696
PMC PMC8645768
MeSH Animals Antineoplastic Agents / therapeutic use* Carcinogenesis / genetics* Carcinogenesis / metabolism Cell Line Cell Line, Tumor Drug Resistance, Neoplasm / genetics* Epithelial-Mesenchymal Transition / genetics Gene Expression Profiling / methods Gene Expression Regulation, Neoplastic* HEK293 Cells Humans Insulin-Like Growth Factor Binding Protein 2 / genetics* Insulin-Like Growth Factor Binding Protein 2 / metabolism Mice, Inbred NOD Mice, SCID Neoplastic Stem Cells / metabolism Pancreatic Neoplasms / drug therapy Pancreatic Neoplasms / genetics* Pancreatic Neoplasms / metabolism RNA Interference Snail Family Transcription Factors / genetics* Snail Family Transcription Factors / metabolism Xenograft Model Antitumor Assays / methods
IF 4.966
Human and Animal Cells 293T(RCB2202)