Apelin-13 is an
adipokine known for its growth-inducing effects on human
breast cancer cells in an
estrogen-containing environment. However, the response of these cells to
apelin-13 in the absence of
estrogen and its association with the expression of the
apelin receptor (
APLNR) has not yet been investigated. In the present study, we show that the
breast cancer cell line MCF-7 expresses the
APLNR as shown by immunofluorescence and flow cytometry, under conditions of ER
starvation and that culture of these cells in the presence of
apelin-13 results in an increased growth rate and a diminished autophagy flux. Moreover, the binding of
APLNR by
apelin-13 resulted in an increased growth rate (assayed by
AlamarBlue) and a diminished autophagy flux (monitored by
Lysotracker Green). The latter observations were reversed in the presence of exogenous
estrogen. Finally,
apelin-13 induces the deactivation of the apoptotic
kinase AMPK. Taken together, our results show that
APLNR signaling in
breast cancer cells is functional and prevents
tumor growth under conditions of
estrogen starvation. They furthermore suggest an alternative mechanism of
estrogen-independent
tumor growth thereby positioning the
APLNR-AMPK axis as a novel pathway and a possible therapeutic target in endocrine resistance of
breast cancer cells.