RILP suppresses invasion of breast cancer cells by modulating the activity of RalA through interaction with RalGDS.

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.

• Authors: Z Wang, Y Zhou, X Hu, W Chen, X Lin, L Sun, X Xu, W Hong, T Wang
• Journal: Cell death & disease (Cell Death Dis) Vol. 6 Pg. e1923 (Oct 15 2015) ISSN: 2041-4889 [Electronic] England
• PMID: 26469971 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• RILP protein, human
• ral Guanine Nucleotide Exchange Factor
• RALA protein, human
• ral GTP-Binding Proteins

Topics

• Adaptor Proteins, Signal Transducing (physiology)
• Breast Neoplasms (metabolism, 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 GTP-Binding Proteins (metabolism)
• ral Guanine Nucleotide Exchange Factor (chemistry, metabolism)