Intestinal phenotype is maintained by Atoh1 in the cancer region of intraductal papillary mucinous neoplasm
| Autor: | Kiichiro Tsuchiya, Yoshihito Kano, Nobuhiro Katsukura, Mamoru Watanabe, Tomoaki Shirasaki, Minoru Tanabe, Susumu Kirimura, Sho Watanabe, Keiichi Akahoshi, Masanobu Kitagawa, Ryuichi Okamoto, Shuji Hibiya, Takumi Akashi |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Cancer Research intestinal type endocrine system diseases Pancreatic Intraductal Neoplasms medicine.disease_cause 03 medical and health sciences Mice 0302 clinical medicine GPA33 Pancreatic cancer Cell Line Tumor Carcinoma medicine Pathology Basic Helix-Loop-Helix Transcription Factors Animals Humans Aged Aged 80 and over Membrane Glycoproteins Intraductal papillary mucinous neoplasm business.industry Atoh1 intraductal papillary mucinous neoplasm Cancer Cell Differentiation General Medicine Original Articles differentiation Middle Aged medicine.disease Phenotype Intestines 030104 developmental biology Oncology Tumor progression 030220 oncology & carcinogenesis Cancer research Heterografts Original Article Female business Carcinogenesis |
| Zdroj: | Cancer Science |
| ISSN: | 1349-7006 1347-9032 |
| Popis: | Intraductal papillary mucinous neoplasm (IPMN) is a precancerous lesion of pancreatic cancer. Although there are 4 types of IPMN, among which intestinal‐type IPMN is likely to progress into invasive cancer known as colloid carcinoma, no information regarding the involvement of the intestinal phenotype in the carcinogenesis of IPMN exists. The present study was conducted to explore how the intestinal differentiation system is maintained during the tumor progression of intestinal‐type IPMN using surgical resection specimens. Results showed that Atoh1, a critical transcriptional factor for intestinal differentiation toward the secretory lineages of intestinal epithelial cells, was expressed in an invasive‐grade IPMN. To determine the function of Atoh1 in pancreatic cancer, we generated a pancreatic ductal adenocarcinoma (PDAC) cell line overexpressing Atoh1. In a xenograft model, we successfully induced an IPMN phenotype in PDAC cells via Atoh1 induction. Finally, for the first time, we discovered that GPA33 is expressed in intestinal‐type IPMN, thereby suggesting a novel target for cancer therapy. In conclusion, the intestinal differentiation system might be maintained during tumor progression of intestinal‐type IPMN. Further analysis of the function of Atoh1 in IPMN might be useful for understanding the molecular mechanism underlying the malignant potential during the tumor progression of IPMN. No information regarding the involvement of the intestinal phenotype in the carcinogenesis of IPMN exists. The present study showed that Atoh1, a critical transcriptional factor for intestinal differentiation, was expressed in an invasive‐grade IPMN. We successfully induced a IPMN phenotype in PDAC cells via Atoh1 induction, resulting in the discovery of a novel target for cancer therapy. |
| Databáze: | OpenAIRE |
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