Back to Search
Start Over
Autocrine Motility Factor Modulates EGF-Mediated Invasion Signaling
- Source :
- Cancer Research. 74:2229-2237
- Publication Year :
- 2014
- Publisher :
- American Association for Cancer Research (AACR), 2014.
-
Abstract
- Autocrine motility factor (AMF) enhances invasion by breast cancer cells, but how its secretion and effector signaling are controlled in the tumor microenvironment is not fully understood. In this study, we investigated these issues with a chimeric AMF that is secreted at high levels through a canonical endoplasmic reticulum (ER)/Golgi pathway. Using this tool, we found that AMF enhances tumor cell motility by activating AKT/ERK, altering actin organization, and stimulating β-catenin/TCF and activating protein 1 transcription. EGF enhanced secretion of AMF through its casein kinase II–mediated phosphorylation. RNA interference–mediated attenuation of AMF expression inhibited EGF-induced invasion by suppressing extracellular signal–regulated kinase signaling. Conversely, exogenous AMF overcame the inhibitory effect of EGF receptor inhibitor gefitinib on invasive motility by activating HER2 signaling. Taken together, our findings show how AMF modulates EGF-induced invasion while affecting acquired resistance to cytotoxic drugs in the tumor microenvironment. Cancer Res; 74(8); 2229–37. ©2014 AACR.
- Subjects :
- MAPK/ERK pathway
Cancer Research
Autocrine Motility Factor
MAP Kinase Signaling System
Motility
Breast Neoplasms
Biology
Transfection
Article
Phosphatidylinositol 3-Kinases
Cytochrome P-450 Enzyme System
Cell Movement
Cell Line, Tumor
Tumor Microenvironment
Humans
Secretion
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
Protein kinase B
beta Catenin
Tumor microenvironment
Epidermal Growth Factor
fungi
Glucose-6-Phosphate Isomerase
Cell biology
Intramolecular Oxidoreductases
Transcription Factor AP-1
Oncology
Cancer research
Casein kinase 1
Proto-Oncogene Proteins c-akt
Subjects
Details
- ISSN :
- 15387445 and 00085472
- Volume :
- 74
- Database :
- OpenAIRE
- Journal :
- Cancer Research
- Accession number :
- edsair.doi.dedup.....c8e687877c5c3406ad7afdc52beacafc