Reference - Detail
| 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 |
| Altmetric score |
オルトメトリクス指標項目
|
| The most frequently cited source | X(Twitter) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | 293T(RCB2202) KLM-1(RCB2138) T3M-4(RCB1021) PK-8(RCB2700) PK-59(RCB1901) |