title: GNG2 inhibits invasion of human malignant melanoma cells with decreased FAK activity.
abstract: It is well known that heterotrimeric G protein is composed of a Gα-subunit and a Gβγ-dimer and promotes cancer characteristics. Our recent study showed reduced G protein γ2 subunit (Gng2/GNG2) expression levels in malignant melanoma cells compared with those in benign melanocytic cells in both mice and humans. Our recent study also showed that reduced GNG2 alone augmented proliferation of malignant melanoma cells. To our knowledge, however, there is no evidence showing an effect of Gng2/GNG2 alone on metastasis of any cancers including malignant melanoma. In his study, we first prepared GNG2-overexpressed SK-Mel28 human malignant melanoma cells, in which GNG2 protein expression level was undetectably low. Migration and invasion activities of the GNG2-overexpressed malignant melanoma cells were suppressed up to 1/10th, with decreased activity of focal adhesion kinase (FAK). We then found that the expression level of GNG2 in A375M, a highly metastatic cell line, was significantly lower than that in A375P, the parental cell line of A375M. We finally showed that knockdown of GNG2 alone in A375P cells enhanced migration and invasion with increased FAK activity. Taken together, our results suggest that overexpression of GNG2 alone inhibits metastasis in human malignant melanoma cells with decreased FAK activity. Thus, GNG2 might be a candidate of molecular targets of prevention and therapy for metastasis of malignant melanoma.
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan ; Units of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University Kasugai, Aichi 487-8501, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yajima
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan ; Units of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University Kasugai, Aichi 487-8501, Japan.
authors.forename: Mayuko Y
authors.initials: MY
authors.lastname: Kumasaka
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamanoshita
authors.affiliation: Units of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University Kasugai, Aichi 487-8501, Japan.
authors.forename: Cunchao
authors.initials: C
authors.lastname: Zou
authors.affiliation: Units of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University Kasugai, Aichi 487-8501, Japan.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Ohgami
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan ; Units of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University Kasugai, Aichi 487-8501, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
keywords: G-protein; gamma subunit; invasion; malignant melanoma