C9orf100, a new member of the Dbl-family guanine nucleotide exchange             factors, promotes cell proliferation and migration in hepatocellular carcinoma.
Dbl-family guanine nucleotide exchange factors (GEFs) are important activators of Rho GTPases, which are significantly associated with tumorigenesis and metastasis. The catalytic ability of the Dbl-family GEFs to activate Rho GTPases depends on their Dbl-homology domain followed by a pleckstrin-homology domain. In the present study, we showed that C9orf100, a new member of the Dbl-family GEFs with a minimal catalytic unit, may contribute to hepatocellular carcinoma (HCC). Quantitative real-time PCR results demonstrated that C9orf100 was highly and widely upregulated in 42/44 (95.5%, >2‑fold) HCC specimens compared with adjacent non-cancerous livers, and this upregulation was correlated with intrahepatic metastasis and α-fetoprotein levels of HCC. Furthermore, the ectopic expression of C9orf100 promoted cell proliferation and colony formation in Huh-7 and YY-8103 cells, whereas silencing of C9orf100 resulted in the suppression of cell growth in MHCC-97H and PLC/PRF/5 cells. Flow cytometry confirmed this effect on MHCC-97H cell growth and indicated that C9orf100 may function in the G2/M phase. In addition, we showed that C9orf100 is involved in the positive regulation of HCC cell migration by a transwell chamber analysis. Our findings suggest that C9orf100 plays a potential oncogenic role in the development and metastasis of HCC.
Department of Hepatobiliary Surgery, Wuxi People's Hospital of Nanjing Medical University, Jiangsu, PR China.
Haixiao
H
Wang
Yandong
Y
Li
Yuping
Y
Wang
Ze-Guang
ZG
Han
Bing
B
Cai
D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*
D020662:Guanine Nucleotide Exchange Factors; D009363:Neoplasm Proteins