期刊
CANCER LETTERS
卷 508, 期 -, 页码 47-58出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2021.03.016
关键词
Pancreatic cancer; Perineural invasion; CD74; GDNF
类别
资金
- National Natural Science Foundation of China [81401931, 81602414, 81702739, 81802317]
- Science and Technology funds of School of Medicine, Shanghai Jiao Tong University [14XJ10022]
- Scientific research project of Shanghai Municipal Health and Family Planning Commission [201740218]
The study revealed that the expression level of CD74 in pancreatic ductal adenocarcinoma is an independent predictor of PNI and poor prognosis, with CD74 enhancing migration and invasion capabilities of PDAC by promoting GDNF production to facilitate neuroplasticity in the microenvironment.
Perineural invasion (PNI) is a common feature of pancreatic ductal adenocarcinoma (PDAC) and is one of the important causes of local recurrence in resected pancreatic cancer, but the molecular mechanism remains largely unexplored. Here, we used immunohistochemistry staining to determine the expression of CD74. Then the in vivo PNI model, in vitro neuroplasticity assay, cell proliferation assay, wound healing and Transwell-based invasion assay were performed to examine the function of CD74 in pancreatic cancer cell lines. ChIP assay and Luciferase reporter assay were used to illustrate the mechanism underlying CD74 induced GDNF expression. We confirmed that the expression level of CD74 was an independent predictor of PNI and poor prognosis for PDAC. Moreover, we found that upregulation of CD74 on PDAC enhanced its migration and invasive capabilities and potentiated the secretion of neurotrophic factor GDNF to promote the neuroplasticity. Mechanistically, CD74 promoted GDNF production via the AKT/EGR-1/GDNF axis in PDAC. Taken together, our findings suggest a supportive role of CD74 in the PNI of PDAC, and deepen our understanding of how cancer cells promote neuroplasticity in the microenvironment of PDAC.
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