Chemokine C-X-C motif receptor 6 contributes to cell migration during hypoxia.
The chemokine and chemokine receptor families have important roles in tumorigenesis. Although CXCR4 and CCR7 have been reported to be associated with cancer metastasis, the role of other chemokine receptors in cancer is poorly understood. We explored the status of CXCR6 in hypoxia-induced cell migration. Breast cancer cells and human umbilical vein endothelial cells (HUVEC) expressed CXCR6, and showed appreciable chemotactic migration to CXCL16. Significant accumulation of CXCR6 mRNA and protein during hypoxia was observed. Overexpression of CXCR6 increased cell migration, and knockdown of CXCR6 attenuated hypoxia-mediated cell migration and MMP-2 secretion. To investigate possible mechanisms regulating CXCR6 expression during hypoxia, we detected the expression of HIFs and found that HIF-1alpha was involved in CXCR6 regulation. CXCR6 and HIF-1alpha were highly expressed in breast cancer lymph nodes metastases. Our data suggest CXCR6 contributes significantly to cell migration during hypoxia.
Lin
Sensen
S
National New Drug Screening Lab, China Pharmaceutical University, Nanjing 210009, PR China.
Sun
Li
L
Hu
Jialiang
J
Wan
Shuying
S
Zhao
Renping
R
Yuan
Shengtao
S
Zhang
Luyong
L
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002633:Chemotaxis; D042783:Endothelial Cells / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000276:immunology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008207:Lymphatic Metastasis; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008875:Middle Aged; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
C106330:CXCR6 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D011991:Receptors, Virus; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2