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Distinct subgroup of the Ras family member 3 (DIRAS3) expression impairs metastasis and induces autophagy of gastric cancer cells in mice.
- Source :
-
Journal of Cancer Research & Clinical Oncology . Oct2018, Vol. 144 Issue 10, p1869-1886. 18p. - Publication Year :
- 2018
-
Abstract
- Purpose: Distinct subgroup of the Ras family member 3 (DIRAS3), also called Aplasia Ras homolog member I, is a tumor suppressor gene that induces autophagy in several cancer cell lines.Methods: This study analyzed DIRAS3, and markers of autophagy (p62, and LC3B-II) in surgically resected GC samples from 420 patients. The promotion of autophagy by DIRAS3 in gastric cancer (GC) cells was explored, which might explain its inhibitory role in gastric cancer cells.Results: DIRAS3 expression in GC was positively correlated with LC3B-II amount, and negatively with metastasis; DIRAS3 and p62 levels were independent prognostic factors in GC. Overexpression of DIRAS3 in BGC-823 cells induced autophagy, led to decreased proliferation, cell cycle arrest in G0/G1 phase, increased apoptosis, and impaired migration and invasion. While knockdown of DIRAS3 promoted proliferation and migration in MKN-45 cells. Overexpression of DIRAS3 in BGC-823 cells elevated autophagy levels in subcutaneous xenograft and inhibited tumor growth in mice; the hematogenous liver and lung metastasis of cancer cells were also suppressed.Conclusions: In conclusion, the results suggest DIRAS3 may play a role in affecting proliferation and metastatic potential of GC cells, which may be associated with its involvement in autophagy regulation. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01715216
- Volume :
- 144
- Issue :
- 10
- Database :
- Academic Search Index
- Journal :
- Journal of Cancer Research & Clinical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 131927820
- Full Text :
- https://doi.org/10.1007/s00432-018-2708-3