The role of hERG1 K+ channels and a functional link between hERG1 K+ channels and SDF-1 in acute leukemic cell migration.
Stromal cell-derived factor-1 (SDF-1) and its unique receptor, CXCR4, regulate stem/progenitor cell migration and retention in the bone marrow and are required for hematopoiesis. Recent studies found that hERG1 K(+) channels were important regulators of tumor cell migration. In this study, we investigated whether SDF-1 induced acute leukemic cell migration associated with hERG1 K(+) channels. Our results showed that E-4031, a specific hERG1 K(+) channels inhibitor, significantly blocked SDF-1-induced migration of leukemic cell lines, primary acute leukemic cells, leukemic stem cells and HEK293T cells transfected with herg-pEGFP. The migration of phenotypically recognizable subsets gave the indication that lymphoblastic leukemic cells were inhibited more than myeloid cells while in the presence of E-4031 which maybe associated with herg expression. SDF-1 increased hERG1 K(+) current expressed in oocytes and HEK293T cells transfected with herg-pEGFP. There were no significant changes of CXCR4 expression on both HL-60 cells and primary leukemic cells regardless if untreated or treated with E-4031 for 24 h (P>0.05). The hERG1 K(+) current increased by SDF-1 might contribute to the mechanism of SDF-1-induced leukemic cell migration. The data suggested that hERG1 K(+) channels functionally linked to cell migration induced by SDF-1.
Li
Huiyu
H
Center for Stem Cell Research and Application, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
Du
Yi-Mei
YM
Guo
Linlin
L
Jie
Shenghua
S
Zhang
Songyu
S
Du
Wen
W
Chen
Xiangjun
X
Liu
Wei
W
Fan
Lingling
L
Zhu
Jiang
J
Zou
Anruo
A
Huang
Shiang
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D054377:Chemokine CXCL12 / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000502:physiology; D009865:Oocytes / Q000166:cytology / Q000502:physiology; D010880:Piperidines / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D014982:Xenopus laevis; D055815:Young Adult
D000889:Anti-Arrhythmia Agents; D054377:Chemokine CXCL12; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D010880:Piperidines; D011725:Pyridines; D019718:Receptors, CXCR4; C063968:E 4031