Diacylglycerol kinase is required for HGF-induced invasiveness and anchorage-independent growth of MDA-MB-231 breast cancer cells.
BACKGROUND
Estrogen receptor (ER)-negative breast cancers have a worse prognosis than ER-positive cancers, being more aggressive and overexposed to stimuli leading to their progression. Hepatocyte growth factor (HGF) has been associated with proliferation, migration and invasion of tumor cells, and several tumors, including those of breast cancer, produce HGF and overexpress its receptor. Diacylglycerol kinases (Dgks), which phosphorylate diacylglycerol to phosphatidic acid, are key regulators of cell signaling. Our research was focused on their role in HGF-induced invasion of MDA-MB-231 cells, a model of ER-negative breast cancer.


METHODS
Dgk activity was evaluated with a kinase assay, MDA-MB-231 cell invasion via culturing of cells in matrigel-coated transwells, and anchorage-independent growth was assessed using a soft agar assay.


RESULTS
HGF induces Dgk activation in MDA-MB-231 cells that is required for cell invasiveness. Moreover, Dgks are involved in MDA-MB-231 anchorage-independent growth.


CONCLUSIONS
Dgks could be a target for ER-negative breast cancer therapy.
Filigheddu
Nicoletta
N
Department of Clinical and Experimental Medicine, University of Piemonte Orientale "A. Avogadro", Via Solaroli 17, 28100 Novara, Italy. nicoletta.filigheddu@med.unipmn.it
Cutrupi
Santina
S
Porporato
Paolo Ettore
PE
Riboni
Francesca
F
Baldanzi
Gianluca
G
Chianale
Federica
F
Fortina
Elisabetta
E
Piantanida
Paola
P
De Bortoli
Michele
M
Vacca
Giovanni
G
Graziani
Andrea
A
Surico
Nicola
N
D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002465:Cell Movement; D019852:Diacylglycerol Kinase / Q000032:analysis / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D009361:Neoplasm Invasiveness; D011960:Receptors, Estrogen / Q000032:analysis / Q000378:metabolism
D011960:Receptors, Estrogen; D017228:Hepatocyte Growth Factor; D019852:Diacylglycerol Kinase