DRG1 is a potential oncogene in lung adenocarcinoma and promotes tumor progression via spindle checkpoint signaling regulation.
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.
Department of Experimental Pathology, Beijing Institute of Radiation Medicine, Beijing, China.
Li
L
Lu
Department of Breast Surgery, QiLu Hospital of Shandong University, Jinan, Shandong, China.
Yanrong
Y
Lv
Department of Experimental Pathology, Beijing Institute of Radiation Medicine, Beijing, China.
Ji
J
Dong
Department of Experimental Pathology, Beijing Institute of Radiation Medicine, Beijing, China.|Hospital of PLA 96164 Troop, Jinhua, Zhejiang, China.
Shaohua
S
Hu
Department of Experimental Pathology, Beijing Institute of Radiation Medicine, Beijing, China.
Ruiyun
R
Peng
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D020090:Chromosome Segregation / Q000235:genetics; D018450:Disease Progression; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D059566:M Phase Cell Cycle Checkpoints; D008938:Mitosis; D009857:Oncogenes; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism
D000970:Antineoplastic Agents; C078418:developmentally regulated GTP-binding protein; D019204:GTP-Binding Proteins
chemoresistance; developmentally regulated GTP-binding protein 1; lung adenocarcinoma; spindle checkpoint