PT  - JOURNAL ARTICLE
AU  - Wen-Cheng Chung
AU  - Lavanya Challagundla
AU  - Yunyun Zhou
AU  - Min Li
AU  - Azeddine Atfi
AU  - Keli Xu
TI  - Loss of <em>Jag1</em> cooperates with oncogenic <em>Kras</em> to induce pancreatic cystic neoplasms
AID  - 10.26508/lsa.201900503
DP  - 2021 Feb 01
TA  - Life Science Alliance
PG  - e201900503
VI  - 4
IP  - 2
4099  - https://www.life-science-alliance.org/content/4/2/e201900503.short
4100  - https://www.life-science-alliance.org/content/4/2/e201900503.full
SO  - Life Sci. Alliance2021 Feb 01; 4
AB  - Notch signaling exerts both oncogenic and tumor-suppressive functions in the pancreas. In this study, deletion of Jag1 in conjunction with oncogenic KrasG12D expression in the mouse pancreas induced rapid development of acinar-to-ductal metaplasia and early stage pancreatic intraepithelial neoplasm; however, culminating in cystic neoplasms rather than ductal adenocarcinoma. Most cystic lesions in these mice were reminiscent of serous cystic neoplasm, and the rest resembled intraductal papillary mucinous neoplasm. Jag1 expression was lost or decreased in cystic lesions but retained in adenocarcinoma in these mice, so was the expression of Sox9. In pancreatic cancer patients, JAG1 expression is higher in cancerous tissue, and high JAG1 is associated with poor overall survival. Expression of SOX9 is correlated with JAG1, and high SOX9 is also associated with poor survival. Mechanistically, Jag1 regulates expression of Lkb1, a tumor suppressor involved in the development of pancreatic cystic neoplasm. Collectively, Jag1 can act as a tumor suppressor in the pancreas by delaying precursor lesions, whereas loss of Jag1 promoted a phenotypic switch from malignant carcinoma to benign cystic lesions.