DRG1 is a potential oncogene in lung adenocarcinoma and promotes tumor progression via spindle checkpoint signaling regulation

Abstract

Developmentally regulated GTP binding protein 1 (DRG1), a member of the DRG family, plays important roles in regulating cell growth. However, the molecular basis of DRG1 in cell proliferation regulation and the relationship between DRG1 and tumor progression remain poorly understood. Here, we demonstrate that DRG1 is elevated in lung adenocarcinomas while weakly expressed in adjacent lung tissues. DRG1 knockdown causes growth inhibition of tumor cells by significantly increasing the proportion of cells in M phase. Overexpression of DRG1 leads to chromosome missegregation which is an important index for tumorigenesis. Interestingly, ectopic of DRG1 reduces taxol induced apoptosis of lung adenocarcinoma cells. Mechanistic analyses confirm that DRG1 localizes at mitotic spindles in dividing cells and binds to spindle checkpoint signaling proteins in vivo. These studies highlight the expanding role of DRG1 in tumorigenesis and reveal a mechanism of DRG1 in taxol resistance.