| 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
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
|
| Resource |
| Human and Animal Cells |
293T(RCB2202)
KLM-1(RCB2138)
T3M-4(RCB1021)
PK-8(RCB2700)
PK-59(RCB1901) |
