Abstract
Ras-related protein Rab-38 (RAB38) is a member of the Ras small G protein family that regulates intracellular vesicular trafficking. Although the expression of RAB38 is reportedly deregulated in several types of cancer, its role in tumor biology remains to be elucidated. In the present study, the expression of RAB38 was analyzed in tumor specimens from patients with non-small cell lung cancer (NSCLC) with tumor recurrence within 4 years (Group R), and those remaining disease-free following initial surgery (Group NR), by reverse transcription-semi-quantitative PCR and subsequent semi-quantification using ImageJ v4.0 software. The results revealed that the expression of RAB38 in Group R and NR specimens was positively associated with tumor recurrence; a high expression level was also associated with poor survival rate in these patients. Using NSCLC cell lines, it was demonstrated that tumor cells with mutations in the active epidermal growth factor receptor (EGFR) gene expressed higher levels of RAB38 compared with those with the wild-type gene by reverse transcription-PCR and western blot analysis. Furthermore, following specific RAB38 gene knockdown by short hairpin RNA transfection, EGFR mutants exhibited markedly reduced invasiveness when compared with cells transfected with empty vector controls by Matrigel Transwell assays. These results suggest that RAB38 is an important prognostic factor in NSCLC, and may serve a critical role in NSCLC-associated tumor metastasis.