Downregulation of the gli transcription factors regulator Kif7 facilitates cell survival and migration of choriocarcinoma cells

• Published in: PloS one 2014-09, Vol.9 (9), p.e108248-e108248
• Main Authors: Ho, Joanna, Du, Yanan, Wong, Oscar Gee-Wan, Siu, Michelle K Y, Chan, Karen K L, Cheung, Annie N Y
• Format: Article
• Language: English
• Subjects: Aberration; Apoptosis; Apoptosis - genetics; Biology and Life Sciences; Biotechnology; Cancer; Cell adhesion & migration; Cell Line; Cell migration; Cell Movement; Cell number; Cell Proliferation - genetics; Cell survival; Cell Survival - genetics; Choriocarcinoma; Choriocarcinoma - genetics; Down-Regulation; Drosophila; Ectopic expression; Female; Gene Expression Regulation, Neoplastic; Gynecology; Hedgehog protein; Humans; Hydatidiform mole; Hydatidiform Mole - genetics; Insects; Kinesin; Kinesin - biosynthesis; Kruppel-Like Transcription Factors - biosynthesis; Ligands; Mammals; Medicine and Health Sciences; Mutation; Nerve Tissue Proteins - biosynthesis; Nuclear Proteins - biosynthesis; Obstetrics; Pathogenesis; Pathology; Placenta - pathology; Pregnancy; Proteins; RNA Interference; RNA, Small Interfering; Signal transduction; Signal Transduction - genetics; Signaling; Solid tumors; Stem cells; Suctioning; Survival; Transcription factors; Transcription Factors - biosynthesis; Trophoblastic disease; Trophoblasts; Trophoblasts - pathology; Tumors; Zinc Finger Protein GLI1; Zinc Finger Protein Gli2; Zinc Finger Protein Gli3
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0108248

The kinesin protein Kif7 has been recognized as an integral component of hedgehog signalling. Aberrant activation of hedgehog signalling has been implicated in many human solid tumours. Gestational trophoblastic disease includes frankly malignant choriocarcinoma and potentially malignant hydatidiform mole. Here we investigated the hedgehog signalling components expression profiles in gestational trophoblastic disease. Downregulation of Gli1, Gli2, Gli3 and Kif7 was demonstrated in clinical samples of choriocarcinoma and hydatidiform moles as well as choriocarcinoma cell lines when compared with normal placentas. Ectopic expression of Kif7 in two choriocarcinoma cell lines JAR and JEG-3 led to a decrease in cell growth and increase in apoptosis demonstrated by MTT and TUNEL assays, respectively. Overexpression of Kif7 also led to suppressed cell migration through transwell assay. In contrast, knocking down Kif7 in HTR-8/SVneo, an immortalized trophoblast cell line, increased cell number over time and increased the migratory ability of the cells. Taken together, Kif7 may contribute to pathogenesis of gestational trophoblastic disease through enhancing survival and promoting dissemination of trophoblasts.