J Cancer 2020; 11(11):3246-3255. doi:10.7150/jca.40953 This issue

Research Paper

The JAM-B/c-src/MMP9 pathway is associated with progression and regulates the invasion of pancreatic cancer

Wunai Zhang1,2*, Rui He3*, Shuo Chen1, Li Zhang1, Gang Cao1, Wenbin Yang1✉, Junhui Li1✉

1. Department of General Surgery, Second Affiliated Hospital, Xi'an Jiaotong University, 157 West 5 th Road, Xi'an, 710004, China.
2. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
3. Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5 th Road, Xi'an, 710004, China.
*These authors have contributed equally to this work.

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Citation:
Zhang W, He R, Chen S, Zhang L, Cao G, Yang W, Li J. The JAM-B/c-src/MMP9 pathway is associated with progression and regulates the invasion of pancreatic cancer. J Cancer 2020; 11(11):3246-3255. doi:10.7150/jca.40953. Available from https://www.jcancer.org/v11p3246.htm

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Abstract

Junctional adhesion molecule B (JAM-B) is a multifunctional transmembrane protein that plays an important role in tumor progression. JAM-B is significantly upregulated in gastric cancer, melanoma cell metastasis and oral squamous cell carcinoma. JAM-2 may also function as a putative tumor suppressor in the progression and metastasis of colorectal cancer. The inconsistency of the results in different cancers has led to uncertainty regarding the role of JAM-B in carcinogenesis. For this purpose, the expression levels of JAM-B in pancreatic cancer (PanCa) tissues were associated with T stage and lymph node involvement with significant differences. A relatively high expression of JAM-B was found in PanCa cell lines by immunohistochemistry and western blot analysis. By cell transfection, JAM-B was silenced in tumor cell lines to determine cell invasion and migration abilities. Scratch wound assays and Transwell assays revealed that shJAM-B significantly decreased Panc-1 cell migration and invasion. Experiments were also conducted using a subcutaneous PanCa nude mouse model. A significant difference in tumor diameter at the injection site was found between the control group and the JAM-B low expression group. The expression levels of c-Src and MMP9 were also significantly reduced compared to that in the control group by immunohistochemistry. In conclusion, our results suggest that JAM-B secreted by cancer cells can promote progression and invasion in PanCa by upregulating the c-Src signal and related downstream proteins.

Keywords: JAM-B, c-src, pancreatic cancer, progression, invasion