ABSTRACT

Desmogleins (DSGs), with the ability to link adjacent cells, have been shown to participate in the development of malignancy. DSG3 was up-regulated in various cancers, including lung, head and neck, and esophagus squamous cell carcinoma, which contributed to the tumor progression. The role of DSG3 in pancreatic ductal adenocarcinoma (PDAC) still remains elusive. Here, the expression of DSG3 was found to be enhanced in pancreatic cancer cell lines in vitro. Functional assays showed that shRNA-mediated knockdown of DSG3 decreased cell viability of pancreatic cancer cells and retarded the cell proliferation, migration and invasion. However, pcDNA-mediated over-expression of DSG3 exhibited reversed effect on pancreatic cancer cell progression. In addition, the in vivo assay demonstrated that transfection of shDSG3 lentiviruses into pancreatic cancer cells repressed the tumorigenicity of PDAC after the cancer cells were transplanted into mice subcutaneously. Elevated DSG3 expression promoted the phosphorylation of Src (p-Src), focal adhesion kinase (p-FAK) and AKT (p-AKT) in vitro, while silence of DSG3 reduced the expression of p-Src, p-FAK and p-AKT both in vitro and in vivo. In conclusion, DSG3, as an oncogene, contributed to the tumorigenicity of PDAC through activating Src–FAK signaling.

摘要

桥粒芯糖蛋白 (DSG) 具有连接相邻细胞的能力，已被证明参与恶性肿瘤的发展。DSG3 在多种癌症中表达上调，包括肺癌、头颈癌和食道鳞状细胞癌，这有助于肿瘤进展。DSG3 在胰腺导管腺癌 (PDAC) 中的作用仍不清楚。在此，发现 DSG3 的表达在体外胰腺癌细胞系中增强。功能测定表明，shRNA 介导的 DSG3 敲低降低了胰腺癌细胞的细胞活力，并延缓了细胞增殖、迁移和侵袭。然而，pcDNA 介导的 DSG3 过度表达对胰腺癌细胞的进展表现出相反的作用。此外，体内实验表明，将shDSG3慢病毒转染胰腺癌细胞后，将癌细胞皮下移植到小鼠体内后，可抑制PDAC的致瘤性。DSG3 表达升高促进了体外Src (p-Src)、粘着斑激酶 (p-FAK) 和 AKT (p-AKT) 的磷酸化，而 DSG3 沉默则降低了 p-Src、p-FAK 和 p- 的表达。 AKT在体外和体内均有效。总之，DSG3 作为癌基因，通过激活 Src-FAK 信号传导导致 PDAC 的致瘤性。