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Updated: Jun 20, 2025

In Vitro Modeling of Cancerous Neural Invasion: The Dorsal Root Ganglion Model
Published on: April 12, 2016
GDNF-induced phosphorylation of MUC21 promotes pancreatic cancer perineural invasion and metastasis by activating
Yutong Chen1,2,3, Weiyu Zhang2,3,4, Yan Zeng1
1Cancer Center of the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, 519000, Guangdong Province, China.
Abstract:
Perineural invasion (PNI) is an adverse prognostic feature of pancreatic ductal adenocarcinoma (PDAC). However, the understanding of the interactions between tumors and neural signaling within the tumor microenvironment is limited. In the present study, we found that MUC21 servers as an independent risk factor for poor prognosis in PDAC. Furthermore, we demonstrated that MUC21 promoted the metastasis and PNI of PDAC cells by activating JNK and inducing epithelial-mesenchymal transition (EMT). Mechanistically, glial cell-derived neurotrophic factor, secreted by Schwann cells, phosphorylates the intracellular domain S543 of MUC21 via CDK1 in PDAC cells, facilitating the interaction between MUC21 and RAC2. This interaction leads to membrane anchoring and activation of RAC2, which in turn activates the JNK/ZEB1/EMT axis, ultimately enhancing the metastasis and PNI of PDAC cells. Our results present a novel mechanism of PNI, suggesting that MUC21 is a potential prognostic marker and therapeutic target for PDAC.
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