Nuclear GSK-3 beta and Oncogenic KRas Lead to the Retention of Pancreatic Ductal Progenitor Cells Phenotypically Similar to Those Seen in IPMN

doi:10.3389/fcell.2022.853003

科研成果详情

题名	Nuclear GSK-3 beta and Oncogenic KRas Lead to the Retention of Pancreatic Ductal Progenitor Cells Phenotypically Similar to Those Seen in IPMN
作者	Ding, Li 1; Roeck, Kaely 1; Zhang, Cheng 2; Zidek, Brooke 1; Rodman, Esther 1; Hernandez-Barco, Yasmin 3; Zhang, Jin-San1,4; Bamlet, William 5; Oberg, Ann 5; Zhang, Lizhi 6; Bardeesy, Nabeel 3; Li, Hu 2; Billadeau, Daniel 1
发表日期	2022-05-13
发表期刊	FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	GSK-3 beta KRAS AQP5 progenitor cell intraductal papillary mucinous neoplasm pancreatic adenocarcinoma
其他关键词	STEM-CELLS ; EXOCRINE PANCREAS ; SELF-RENEWAL ; BETA-CELLS ; IN-VITRO ; CANCER ; GLYCOGEN-SYNTHASE-KINASE-3-BETA ; MAINTENANCE ; EXPRESSION ; REGULATOR
摘要	Glycogen synthase kinase-3 beta (GSK-3 beta) is a downstream target of oncogenic KRas and can accumulate in the nucleus in pancreatic ductal adenocarcinoma (PDA). To determine the interplay between oncogenic KRas and nuclear GSK-3 beta in PDA development, we generated Lox-STOP-Lox (LSL) nuclear-targeted GSK-3 beta animals and crossed them with LSL-KRas(G12D) mice under the control of the Pdx1-cre transgene-referred to as KNGC. Interestingly, 4-week-old KNGC animals show a profound loss of acinar cells, the expansion of ductal cells, and the rapid development of cystic-like lesions reminiscent of intraductal papillary mucinous neoplasm (IPMN). RNA-sequencing identified the expression of several ductal cell lineage genes including AQP5. Significantly, the Aqp5(+) ductal cell pool was proliferative, phenotypically distinct from quiescent pancreatic ductal cells, and deletion of AQP5 limited expansion of the ductal pool. Aqp5 is also highly expressed in human IPMN along with GSK-3 beta highlighting the putative role of Aqp5(+) ductal cells in human preneoplastic lesion development. Altogether, these data identify nGSK-3 beta and KRas(G12D) as an important signaling node promoting the retention of pancreatic ductal progenitor cells, which could be used to further characterize pancreatic ductal development as well as lineage biomarkers related to IPMN and PDA.
资助项目	Pancreatic Cancer SPORE [CA102701]; Center for Biomedical Discovery Pilot Award; Transgenic and Knockout; Genome Analysis Shared Resources of the Mayo Clinic Cancer Center [P30 CA015083]
出版者	FRONTIERS MEDIA SA
出版地	LAUSANNE
ISSN	2296-634X
卷号	10 页码:853003
DOI	10.3389/fcell.2022.853003
页数	15
WOS类目	Cell Biology ; Developmental Biology
WOS研究方向	Cell Biology ; Developmental Biology
WOS记录号	WOS:000804476900001
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	35646902
SCOPUSEID	2-s2.0-85131300823
通讯作者地址	[Ding, Li]Division of Oncology Research,College of Medicine,Mayo Clinic,Rochester,United States ; [Billadeau, Daniel]Division of Oncology Research,College of Medicine,Mayo Clinic,Rochester,United States
Scopus学科分类	Developmental Biology;Cell Biology
引用统计	被引频次[WOS]：0 [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/148084
专题	第一临床医学院（信息与工程学院）、附属第一医院_精准医学中心实验室附属第一医院
通讯作者	Ding, Li; Billadeau, Daniel
作者单位	1.Division of Oncology Research,College of Medicine,Mayo Clinic,Rochester,United States; 2.Department of Molecular and Experimental Therapeutics,College of Medicine,Mayo Clinic,Rochester,United States; 3.Center for Cancer Research,Harvard Medical School,Boston,United States; 4.Center for Precision Medicine,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 5.Department of Health Sciences Research,College of Medicine,Mayo Clinic,Rochester,United States; 6.Department of Laboratory Medicine and Pathology,College of Medicine,Mayo Clinic,Rochester,United States
推荐引用方式 GB/T 7714	Ding, Li,Roeck, Kaely,Zhang, Cheng,et al. Nuclear GSK-3 beta and Oncogenic KRas Lead to the Retention of Pancreatic Ductal Progenitor Cells Phenotypically Similar to Those Seen in IPMN[J]. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,2022,10:853003.
APA	Ding, Li., Roeck, Kaely., Zhang, Cheng., Zidek, Brooke., Rodman, Esther., ... & Billadeau, Daniel. (2022). Nuclear GSK-3 beta and Oncogenic KRas Lead to the Retention of Pancreatic Ductal Progenitor Cells Phenotypically Similar to Those Seen in IPMN. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 10, 853003.
MLA	Ding, Li,et al."Nuclear GSK-3 beta and Oncogenic KRas Lead to the Retention of Pancreatic Ductal Progenitor Cells Phenotypically Similar to Those Seen in IPMN".FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 10(2022):853003.