Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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.

SUBMITTER: Wang Z

PROVIDER: S-EPMC4632296 | biostudies-other | 2015

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

C2ORF40 suppresses breast cancer cell proliferation and invasion through modulating expression of M phase cell cycle genes.

Project description:Recently, it has been suggested that C2ORF40 is a candidate tumor suppressor gene in breast cancer. However, the mechanism for reduced expression of C2ORF40 and its functional role in breast cancers remain unclear. Here we show that C2ORF40 is frequently silenced in human primary breast cancers and cell lines through promoter hypermethylation. C2ORF40 mRNA level is significantly associated with patient disease-free survival and distant cancer metastasis. Overexpression of C2ORF4 0 inhibits breast cancer cell proliferation, migration and invasion. By contrast, silencing C2ORF40 expression promotes these biological phenotypes. Bioinformatics and FACS analysis reveal C2ORF40 functions at G2/M phase by downregulation of mitotic genes expression, including UBE2C. Our results suggest that C2ORF40 acts as a tumor suppressor gene in breast cancer pathogenesis and progression and is a candidate prognostic marker for this disease.

| S-EPMC3857337 | biostudies-literature

Rab26 suppresses migration and invasion of breast cancer cells through mediating autophagic degradation of phosphorylated Src.

Project description:Rab proteins play crucial roles in membrane trafficking. Some Rab proteins are implicated in cancer development through regulating protein sorting or degradation. In this study, we found that the expression of Rab26 is suppressed in the aggressive breast cancer cells as compared to the levels in non-invasive breast cancer cells. Over-expression of Rab26 inhibits cell migration and invasion, while Rab26 knockdown significantly promotes the migration and invasion of breast cancer cells. Rab26 reduces focal adhesion association of Src kinase and induces endosomal translocation of Src. Further experiments revealed that Rab26 mediates the autophagic degradation of phosphorylated Src through interacting with ATG16L1, consequently, resulting in the suppression of the migration and invasion ability of breast cancer cells.

| S-EPMC7969620 | biostudies-literature

HDAC inhibitor suppresses proliferation and invasion of breast cancer cells through regulation of miR-200c targeting CRKL.

Project description:Although histone deacetylase (HDAC) inhibitors have been shown to effectively induce the inhibition of proliferation and migration in breast cancer, the anticancer mechanism remains poorly understood. Our studies show that miR-200c was significantly downregulated in breast cancer cell lines compared to normal cell lines and inversely correlated with the levels of class IIa HDACs and CRKL. HDAC inhibitors and the ectopic expression of miR-200c as tumor suppressors inhibited the proliferation, invasion, and migration of breast cancer cells by downregulating CRKL. These results indicate that the anticancer mechanism of HDAC inhibitor was realized partially by regulating miR-200c via CRKL targeting. Our findings suggest that the HDAC-miR200c-CRKL signaling axis could be a novel diagnostic marker and potential therapeutic target in breast cancer.

| S-EPMC5733635 | biostudies-literature

SIRT1 promotes formation of breast cancer through modulating Akt activity.

Project description:The silent information regulation factor 1 (sirtuin Type 1, SIRT1), as a kind of NAD+ dependent class III histone deacetylation enzyme, has been found to be involved in tumor proliferation, invasion, and metastasis. The roles of SIRTl in breast cancer is multifaceted depending on its substrate from upstream or downstream signaling pathway. In this study, we sought to make clear the regulating effects of SIRT1 in breast cancer cells, and to explore the underlying mechanisms through which SIRT1 regulates breast cancer. First, our results showed that SIRT1 was significantly up-regulated in breast cancer tissues and cells, which correlated with histological grade, tumor size, as well as lymph node metastasis. Then we established SIRT1-overexpressed and SIRT1- knockdown breast cancer cell lines to investigate the functions of SIRT1 in regulating colony formation, cell proliferation, cell cycle, cell apoptosis and migration. We found that overexpression of SIRT1 significantly promoted breast cancer growth both in vitro and in vivo, whereas knockdown of SIRT1 inhibited these phenotypes. Furthermore, SIRT1 was found to interact with Akt directly, consequently promoting the activity of Akt in breast cancer cells in vitro and positively correlating with expression of Akt, P-Akt, in breast cancer tissues in vivo. Down regulation the activity of Akt partially weakened the proliferative effect mediated by SIRT1. Taken together, our results demonstrated SIRT1's tumor promotion function and potential mechanisms in breast cancer, thus providing valuable therapeutic targets for breast cancer.

| S-EPMC5995935 | biostudies-literature

Phospholipase Cδ1 suppresses cell migration and invasion of breast cancer cells by modulating KIF3A-mediated ERK1/2/β- catenin/MMP7 signalling.

Project description:Phospholipase C δ1 (PLCD1) encodes an enzyme involved in energy metabolism, calcium homeostasis and intracellular movement. It is located at 3p22 in a region that is frequently deleted in multiple cancers, and the PLCD1 enzyme is a potential tumour suppressor in breast cancer that inhibits matrix metalloprotease (MMP) 7, but the detailed mechanism remains elusive. In this study, we found that PLCD1 was downregulated in breast cancers, and the gain-or-loss functional assay revealed that PLCD1 inhibited cell migration and invasion in vitro via the ERK1/2/β-catenin/MMP7 signalling pathway. Furthermore, KIF3A was identified as a downstream mediator of PLCD1, and there was an inverse correlation between the expression of PLCD1 and KIF3A. Knockdown of KIF3A expression alone suppressed cell migration and invasion, and attenuated ERK1/2/β-catenin/MMP7 signalling that was reactivated by knocking down PLCD1 in vitro. Collectively, our findings suggest that PLCD1 acts as a tumour suppressor, by KIF3A-mediated suppression of ERK1/2/β-catenin/MMP7 signalling, at least in part, in breast cancer.

| S-EPMC5438712 | biostudies-literature

Fe65 Suppresses Breast Cancer Cell Migration and Invasion through Tip60 Mediated Cortactin Acetylation.

Project description:Fe65 is a brain-enriched adaptor protein known for its role in the action of the Aβ amyloid precursor protein in neuronal cells and Alzheimer's disease, but little is known about its functions in cancer cells. The present study documents for the first time a role of Fe65 in suppressing breast cancer cell migration and invasion. Mechanistic studies suggest that the suppression is mediated through its phosphotyrosine binding domain 1 that mediates the recruitment of Tip60 to cortactin to stimulate its acetylation. The studies identify the Tip60 acetyltransferase as a cytoplasmic drug target for the therapeutic intervention of metastatic breast cancers.

| S-EPMC4499803 | biostudies-literature

Corylin suppresses metastasis of breast cancer cells by modulating miR-34c/LINC00963 target.

Project description:Breast cancer is one of the cancers leading to most death cases among women and metastasis is the major cause of breast cancer mortality. In this study, Corylin, the flavonoid compound which is extracted and purified from Psoralea corylifolia L., the effect on breast cancer metastasis was investigated. Corylin showed inhibitory effect on migration and invasion abilities of breast cancer cells. Meanwhile, the epithelial-mesenchymal transition was also regulated by corylin. The long non-coding RNA LINC00963 was found to have a significantly high expression level in breast cancer while it can be down-regulated by corylin. In addition, both wound-healing assay and transwell assay showed that LINC00963 induced breast cancer cells metastasis. MiR-34c was increased by corylin treatment depending on p53, and it was firstly identified that the LINC00963 was a direct target of miR-34c. Corylin was verified here that it prohibited MCF-7 migration and invasion depending on miR-34c/LINC00963 target. In conclusion, corylin suppresses metastasis of breast cancer cells via increasing miR-34c expression, which was dependent on p53. LINC00963 was a direct target of miR-34c and the target axis was necessary for corylin function. Therefore, corylin is a promising drug candidate and LINC00963 can be seen as a promising target in breast cancer treatment.

| S-EPMC8635637 | biostudies-literature

MTH-3 SUPPRESSES BREAST CANCER INVASION

Project description:Next-generation sequencing analysis reveals that MTH-3, a novel curcuminoid derivative, suppresses the invasion of MDA-MB-231 triple-negative breast adenocarcinoma cells

| PRJEB44027 | ENA

TFPI-2 suppresses breast cancer cell proliferation and invasion through regulation of ERK signaling and interaction with actinin-4 and myosin-9.

Project description:TFPI-2 has been recognized as a potent tumor suppressor gene. Low expression of TFPI-2 results in enhanced growth and metastasis of a variety of human tumors. In the present study, we investigated the mechanism responsible for the tumor suppressive effect of TFPI-2. Overexpression of TFPI-2 decreased phosphorylation of ERK1/2 and the translocation of p-ERK1/2 from cytoplasm into the nucleus, and eventually resulted in a reduced cell proliferation. Immunoprecipitation assays identified myosin-9 and actinin-4 as TFPI-2-interacting proteins. Full-length TFPI-2 was required for binding to actinin-4, whereas the N?+?KD1 regions of TFPI-2 were sufficient to interact with myosin-9. Although overexpression of TFPI-2 or TFPI-2/N?+?KD1 does not affect the expression of actinin-4 and myosin-9, it inhibits the migration and invasion of human breast cancer cells. Our results suggest that TFPI-2 suppresses cancer cell proliferation and invasion partly through the regulation of the ERK1/2 signaling and through interactions with myosin-9 and actinin-4.

| S-EPMC6158255 | biostudies-other

Raddeanin A suppresses breast cancer-associated osteolysis through inhibiting osteoclasts and breast cancer cells.

Project description:Bone metastasis is a severe complication of advanced breast cancer, resulting in osteolysis and increased mortality in patients. Raddeanin A (RA), isolated from traditional Chinese herbs, is an oleanane-type triterpenoid saponin with anticancer potential. In this study, we investigated the effects of RA in breast cancer-induced osteolysis and elucidated the possible mechanisms involved in this process. We first verified that RA could suppress osteoclast formation and bone resorption in vitro. Next, we confirmed that RA suppressed Ti-particle-induced osteolysis in a mouse calvarial model, possibly through inhibition of the SRC/AKT signaling pathway. A breast cancer-induced osteolysis mouse model further revealed the positive protective effects of RA by micro-computed tomography and histology. Finally, we demonstrated that RA inhibited invasion and AKT/mammalian target of rapamycin signaling and induced apoptosis in MDA-MB-231 cells. These results indicate that RA is an effective inhibitor of breast cancer-induced osteolysis.

| S-EPMC5841366 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data