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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091754 | PMC |
| http://dx.doi.org/10.1158/0008-5472.CAN-13-2937 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Immunohistochemical markers of potential utility in identifying POLE-mutant endometrial carcinomas: An assessment of autocrine motility factor (AMF) and autocrine motility factor receptor (AMFR).
Ann Diagn Pathol
January 2025
Akdeniz University, Faculty of Medicine, Department of Pathology, Konyaaltı, 07070 Antalya, Turkey.
POLE status determination is necessary for the molecular classification of endometrial carcinomas (EC). However, this determination is only achievable by molecular techniques, which are not available in many practice settings. A previously published study reported elevated AMF/GPI and AMFR/gp78 levels in POLE-mutant EC.
View Article and Find Full Text PDFExtracellular Vesicles from a Novel Chordoma Cell Line, ARF-8, Promote Tumorigenic Microenvironmental Changes When Incubated with the Parental Cells and with Human Osteoblasts.
Int J Mol Sci
November 2024
Department of Neurosurgery, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Chordomas are rare, generally slow-growing spinal tumors that nonetheless exhibit progressive characteristics over time, leading to malignant phenotypes and high recurrence rates, despite maximal therapeutic interventions. The tumors are notoriously resistant to therapies and are often located in regions that complicate achieving gross total resections. Cell lines from these tumors are rare as well.
View Article and Find Full Text PDFGonadotropin-releasing hormone II and its receptor regulate motility, morphology, and kinematics of porcine spermatozoa in vitro.
Gen Comp Endocrinol
December 2024
University of Nebraska-Lincoln, Department of Animal Science, Lincoln, NE 68583-0908, United States. Electronic address:
The second form of gonadotropin-releasing hormone (GnRH-II) and its receptor (GnRHR-II) are abundantly produced within the porcine testis and immunolocalize within the seminiferous tubules, suggesting a role in spermatogenesis and/or sperm function. The objective of this study was to quantify GnRH-II and GnRHR-II abundance within boar reproductive tract tissues and examine their role in porcine sperm function. Immunoblotting revealed GnRHR-II abundance was 12-fold greater (P < 0.
View Article and Find Full Text PDFAutocrine small extracellular vesicles induce tubular phenotypic transformation in diabetic nephropathy via miR-21-5p.
Gene
February 2025
Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi Province 341000, China; The First School of Clinical Medicine, Gannan Medical University, Ganzhou, Jiangxi Province 341000, China. Electronic address:
Background: Diabetic nephropathy (DN) is one of the most common and serious microvascular complications associated with diabetes. DN is the leading contributor to the majority of cases of end-stage renal disease (ESRD). Small extracellular vesicles (sEVs) can transport various genetic materials to recipient cells.
View Article and Find Full Text PDFToll-Like receptor 3-mediated interferon-β production is suppressed by oncostatin m and a broader epithelial-mesenchymal transition program.
Breast Cancer Res
November 2024
Department of Pathology Case, Western Reserve University, Cleveland, OH, 44106, USA.
Background: Patients with Triple Negative Breast Cancer (TNBC) currently lack targeted therapies, and consequently face higher mortality rates when compared to patients with other breast cancer subtypes. The tumor microenvironment (TME) cytokine Oncostatin M (OSM) reprograms TNBC cells to a more stem-like/mesenchymal state, conferring aggressive cancer cell properties such as enhanced migration and invasion, increased tumor-initiating capacity, and intrinsic resistance to the current standards of care. In contrast to OSM, Interferon-β (IFN-β) promotes a more differentiated, epithelial cell phenotype in addition to its role as an activator of anti-tumor immunity.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!