HOXD3-overexpression increases integrin alpha v beta 3 expression and deprives E-cadherin while it enhances cell motility in A549 cells.
We have previously shown that transduction of HOXD3, one of homeobox genes, into human lung cancer A549 cells enhances cell motility, invasion and metastasis. In the present study, we examined the roles of integrin beta3 which was up-regulated by HOXD3-overexpression in the HOXD3-induced motility of A549 cells. We first established integrin beta3-transfectants and compared their motile activity to those of the HOXD3-transfected, control-transfected and parental cells by three different assays. The integrin beta3-transfectants as well as the HOXD3-transfectants formed heterodimer with integrin alphav subunit, and showed highly motile activities assessed by haptotaxis or phagokinetic track assay compared to the control transfectants or parental cells. In vitro wound-healing assay revealed that migratory activities were graded as the HOXD3-transfectants > the integrin beta3-transfectants > the control transfectants or parental cells. E-cadherin was expressed in the integrin beta3-transfectants but not expressed in the HOXD3-transfectants. An addition of function-blocking antibody to E-cadherin into the wound-healing assay promoted the migratory activity of the integrin beta3-transfectants, suggesting that E-cadherin prevented the cells from dissociating from the wound edges. These results indicate that increased expression of integrin alphav beta3 and loss of E-cadherin by HOXD3-overexpression are responsible for the enhanced motility and dissociation.
Ohta
Hironori
H
Division of Cancer-Related Genes, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo 060-0815, Japan.
Hamada
Jun-ichi
J
Tada
Mitsuhiro
M
Aoyama
Tetsuya
T
Furuuchi
Keiji
K
Takahashi
Yoko
Y
Totsuka
Yasunori
Y
Moriuchi
Tetsuya
T
D000818:Animals; D015820:Cadherins / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000502:physiology*; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000502:physiology*; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D009362:Neoplasm Metastasis; D015398:Signal Transduction; D014157:Transcription Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014945:Wound Healing
D015820:Cadherins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D039302:Integrin alphaVbeta3; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C073547:HOXA4 protein, human