CXCL12-CXCR7 signaling activates ERK and Akt pathways in human choriocarcinoma cells.
Abstract CXCL12 acts as a physiological ligand for the chemokine receptor CXCR7. Chemokine receptor expression by human trophoblast and other placental cells have important implications for understanding the regulation of placental growth and development. We had previously reported the differential expression of CXCR7 in different stages of the human placenta suggesting its possible role in regulation of placental growth and development. In this study, we determined the expression of CXCR7 in human choriocarcinoma JAR cells at the mRNA level and protein level and the downstream signaling pathway mediated by CXCL12-CXCR7 interaction. We observed that binding of CXCL12 to CXCR7 activates the ERK and Akt cell-survival pathways in JAR cells. Inhibition of the ERK and Akt pathways using specific inhibitors (Wortmanin & PD98509) led to the activation of the p38 pathway. Our findings suggest a possible role of CXCR7 in activating the cell survival pathways ERK and Akt in human choriocarcinoma JAR cells.
Department of Biochemistry, All India Institute of Medical Sciences , New Delhi , India.
Vishwas
V
Tripathi
Romsha
R
Kumar
Amit K
AK
Dinda
Jagdeep
J
Kaur
Kalpana
K
Luthra
D045744:Cell Line, Tumor; D002470:Cell Survival; D054377:Chemokine CXCL12 / Q000378:metabolism*; D002822:Choriocarcinoma; D015870:Gene Expression; D006801:Humans; D020935:MAP Kinase Signaling System; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D054387:Receptors, CXCR / Q000235:genetics / Q000378:metabolism*
C501896:ACKR3 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D054387:Receptors, CXCR; D051057:Proto-Oncogene Proteins c-akt
CXCR7; Chemokines; RDC1; SDF-1; chemokine receptor; human placental cells