Abstract
Expression of the chemokine stromal cell-derived factor-1α (SDF-1α) is absent from many carcinomas, including hepatomas. We note an early signalling defect in the hepatocellular carcinoma (HCC) cell line HepG2 that expresses the CXCR4 receptor and binds biotin-labelled SDF, but fails to stimulate downstream signalling events after engagement with SDF. In HepG2, the SDF/CXCR4 interaction did not result in calcium influx, phosphorylation and internalization of CXCR4, nor in a rapid phosphorylation of p44/42 MAP kinase. There were no CXCR4 mutations in the second chemokine binding loop or C terminal phosphorylation and internalization domains. The downstream signalling machinery in HepG2 appears to be intact since transfection of wild-type CXCR4 restored functional responsiveness. We conclude that HepG2 is unresponsive to SDF stimulation because of a defect located after receptor binding but before the activation of the signalling cascade. A hypothetical blocking molecule could hinder receptor internalization or CXCR4 signalling.
| Original language | English |
|---|---|
| Pages (from-to) | 311-319 |
| Number of pages | 9 |
| Journal | Cellular Signalling |
| Volume | 13 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 1 2001 |
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All Science Journal Classification (ASJC) codes
- Cell Biology
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Loss of chemokine SDF-1α-mediated CXCR4 signalling and receptor internalization in human hepatoma cell line HepG2. / Mitra, Prasenjit; De, Asit; Ethier, Michael F.; Mimori, Koshi; Kodys, Karen; Shibuta, Kenji; Mori, Masaki; Madison, J. Mark; Miller-Graziano, Carol; Barnard, Graham F.
In: Cellular Signalling, Vol. 13, No. 5, 01.05.2001, p. 311-319.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Loss of chemokine SDF-1α-mediated CXCR4 signalling and receptor internalization in human hepatoma cell line HepG2
AU - Mitra, Prasenjit
AU - De, Asit
AU - Ethier, Michael F.
AU - Mimori, Koshi
AU - Kodys, Karen
AU - Shibuta, Kenji
AU - Mori, Masaki
AU - Madison, J. Mark
AU - Miller-Graziano, Carol
AU - Barnard, Graham F.
PY - 2001/5/1
Y1 - 2001/5/1
N2 - Expression of the chemokine stromal cell-derived factor-1α (SDF-1α) is absent from many carcinomas, including hepatomas. We note an early signalling defect in the hepatocellular carcinoma (HCC) cell line HepG2 that expresses the CXCR4 receptor and binds biotin-labelled SDF, but fails to stimulate downstream signalling events after engagement with SDF. In HepG2, the SDF/CXCR4 interaction did not result in calcium influx, phosphorylation and internalization of CXCR4, nor in a rapid phosphorylation of p44/42 MAP kinase. There were no CXCR4 mutations in the second chemokine binding loop or C terminal phosphorylation and internalization domains. The downstream signalling machinery in HepG2 appears to be intact since transfection of wild-type CXCR4 restored functional responsiveness. We conclude that HepG2 is unresponsive to SDF stimulation because of a defect located after receptor binding but before the activation of the signalling cascade. A hypothetical blocking molecule could hinder receptor internalization or CXCR4 signalling.
AB - Expression of the chemokine stromal cell-derived factor-1α (SDF-1α) is absent from many carcinomas, including hepatomas. We note an early signalling defect in the hepatocellular carcinoma (HCC) cell line HepG2 that expresses the CXCR4 receptor and binds biotin-labelled SDF, but fails to stimulate downstream signalling events after engagement with SDF. In HepG2, the SDF/CXCR4 interaction did not result in calcium influx, phosphorylation and internalization of CXCR4, nor in a rapid phosphorylation of p44/42 MAP kinase. There were no CXCR4 mutations in the second chemokine binding loop or C terminal phosphorylation and internalization domains. The downstream signalling machinery in HepG2 appears to be intact since transfection of wild-type CXCR4 restored functional responsiveness. We conclude that HepG2 is unresponsive to SDF stimulation because of a defect located after receptor binding but before the activation of the signalling cascade. A hypothetical blocking molecule could hinder receptor internalization or CXCR4 signalling.
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UR - http://www.scopus.com/inward/citedby.url?scp=17344374988&partnerID=8YFLogxK
U2 - 10.1016/S0898-6568(01)00156-5
DO - 10.1016/S0898-6568(01)00156-5
M3 - Article
C2 - 11369512
AN - SCOPUS:17344374988
VL - 13
SP - 311
EP - 319
JO - Cellular Signalling
JF - Cellular Signalling
SN - 0898-6568
IS - 5
ER -