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RILP suppresses invasion of breast cancer cells by modulating the activity of RalA through interaction with RalGDS.
- Source :
-
Cell death & disease [Cell Death Dis] 2015 Oct 15; Vol. 6, pp. e1923. Date of Electronic Publication: 2015 Oct 15. - Publication Year :
- 2015
-
Abstract
- RILP (Rab7-interacting lysosomal protein) is a key regulator for late endosomal/lysosomal trafficking, and probably a tumor suppressor in prostate cancer. However, the role of RILP in other cancers and the underlying mechanism for RILP in regulating the invasion of cancer cells remain to be investigated. In this study, we showed that overexpression of RILP in breast cancer cells inhibits the migration and invasion, whereas the depletion of RILP by RNAi-mediated knockdown promotes the migration and invasion. We identified RalGDS (Ral guanine nucleotide dissociation stimulator) as a novel interacting partner for RILP, and truncation analysis revealed the N-terminal region of RILP is responsible for interacting with the guanine nucleotide exchange factor (GEF) domain of RalGDS. Immunofluorescence microscopy revealed that RalGDS can be recruited to the late endosomal compartments by RILP. Further investigations indicated that the overexpression of RILP inhibits the activity of RalA, a downstream target of RalGDS. Our data suggest that RILP suppresses the invasion of breast cancer cells by interacting with RalGDS to inhibit its GEF activity for RalA.
- Subjects :
- Breast Neoplasms pathology
Cell Movement
Cell Proliferation
Endosomes metabolism
Female
Humans
MAP Kinase Signaling System
MCF-7 Cells
Neoplasm Invasiveness
Protein Binding
Protein Interaction Domains and Motifs
Protein Transport
ral Guanine Nucleotide Exchange Factor chemistry
Adaptor Proteins, Signal Transducing physiology
Breast Neoplasms metabolism
ral GTP-Binding Proteins metabolism
ral Guanine Nucleotide Exchange Factor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-4889
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Cell death & disease
- Publication Type :
- Academic Journal
- Accession number :
- 26469971
- Full Text :
- https://doi.org/10.1038/cddis.2015.266