SNAIL2 contributes to tumorigenicity and chemotherapy resistance in pancreatic cancer by regulating IGFBP2.
Animals
Antineoplastic Agents
/ therapeutic use
Carcinogenesis
/ genetics
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
Mice, Inbred NOD
Mice, SCID
Neoplastic Stem Cells
/ metabolism
Pancreatic Neoplasms
/ drug therapy
RNA Interference
Snail Family Transcription Factors
/ genetics
Xenograft Model Antitumor Assays
/ methods
SNAIL2
cancer stem cells
epithelial-mesenchymal transition
pancreatic cancer
tumor spheroid
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
Dec 2021
Dec 2021
Historique:
revised:
25
09
2021
received:
16
04
2021
accepted:
28
09
2021
pubmed:
11
10
2021
medline:
21
12
2021
entrez:
10
10
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34628696
doi: 10.1111/cas.15162
pmc: PMC8645768
doi:
Substances chimiques
Antineoplastic Agents
0
Insulin-Like Growth Factor Binding Protein 2
0
SNAI1 protein, human
0
Snail Family Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4987-4999Subventions
Organisme : Grants-in-Aid KAKENHI from the Ministry of Education, Culture, Sports, Science, and Technology
ID : 17K09460
Organisme : Sumitomo Dainippon Pharma Inc.
Informations de copyright
© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
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