SEMA7A-mediated juxtacrine stimulation of IGFBP-3 upregulates IL-17RB at pancreatic cancer invasive front.
Journal
Cancer gene therapy
Series/Report No.
Cancer Gene Therapy
Journal Volume
31
Journal Issue
12
Pages
1840 - 1855
ISSN
1476-5500
Date Issued
2024-10-24
Author(s)
Chen, Yi-Ing
Tien, Sui-Chih
Ko, Yi-Ling
Chang, Chin-Chun
Hsu, Min-Fen
Chien, Hung Jen
Peng, Hsuan-Yu
Hu, Chun-Mei
Abstract
Tumor invasion is the hallmark of tumor malignancy. The invasive infiltration pattern of tumor cells located at the leading edge is highly correlated with metastasis and unfavorable patient outcomes. However, the regulatory mechanisms governing tumor malignancy at the invasive margin remain unclear. The IL-17B/IL-17RB pathway is known to promote pancreatic cancer invasion and metastasis, yet the specific mechanisms underlying IL-17RB upregulation during invasion are poorly understood. In this study, we unveiled a multistep process for IL-17RB upregulation at the invasive margin, which occurs through direct communication between tumor cells and fibroblasts. Tumor ATP1A1 facilitates plasma membrane expression of SEMA7A, which binds to and induces IGFBP-3 secretion from fibroblasts. The resulting gradient of IGFBP-3 influences the direction and enhances IL-17RB expression to regulate SNAI2 in invasion. These findings highlight the importance of local tumor-fibroblast interactions in promoting cancer cell invasiveness, potentially leading to the development of new therapeutic strategies targeting this communication.
Publisher
Springer Nature
Type
journal article