CSMD1 exhibits antitumor activity in A375 melanoma cells through activation of the Smad pathway

• DOI: 10.1007/s10495-012-0727-0
• Publication Date: 2012-04-26T01:39:14Z
• Authors: Ming-Rui Tang; Yu-Xin Wang; Shu Guo; Si-Yuan Han; Di Wang
• Keywords: 0301 basic medicine; 0303 health sciences; Neovascularization, Pathologic; Tumor Suppressor Proteins; Membrane Proteins; Apoptosis; Cell Cycle Checkpoints; Mice, SCID; Smad2 Protein; Xenograft Model Antitumor Assays; Smad1 Protein; Mice; 03 medical and health sciences; Mice, Inbred NOD; Cell Line, Tumor; Animals; Humans; Smad3 Protein; Melanoma; Neoplasm Transplantation; Signal Transduction; Smad4 Protein

In this work, we studied the effects of CUB and Sushi multiple domains 1 gene (CSMD1) expression in A375 melanoma cells in vivo and in vitro. CSDM1 expression decreased proliferation and migration, and increased apoptosis and G(1) arrest in A375 cells in vitro. Expression of CSDM1 in established xenografted tumors decreased tumor size and weight, and decreased the density of intratumor microvessels. The survival rate of mice with tumors expressing CSMD1 was significantly higher than mice with tumors that did not express CSDM1. These results confirm the role of CSDM1 as a tumor suppressor gene in melanoma cells. Furthermore, we found that CSMD1 can interact with Smad3, activate Smad1, Smad2, and Smad3, and increase the expression of Smad4. These results might prove helpful for the development of novel therapies for melanoma treatment.