Open AccessMAFIP is a tumor suppressor in cervical cancer that inhibits activation of the nuclear factor‐kappa B pathway
Author(s) -
Li Yang,
Yu Yao,
Zhang Yan,
Zhou Yufei,
Li Chao,
Zhu Jianbing,
Yuan Hanying,
Lu Hong
Publication year - 2011
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2011.02061.x
Subject(s) - hela , suppressor , cancer research , oncogene , cancer , cervical cancer , gene knockdown , nf κb , nfkb1 , tumor suppressor gene , cancer cell , iκbα , tumor progression , biology , carcinogenesis , medicine , chemistry , cell cycle , in vitro , signal transduction , cell culture , microbiology and biotechnology , transcription factor , gene , biochemistry , genetics
Cervical cancer is the second most common cancer in women. Inactivation of tumor suppressor genes underlies the transformation and progression of cervical cancer. Previously, we reported MAFIP can inhibit the growth of human cervical cancer HeLa cells. In this study, MAFIP was found to be downregulated in cervical intraepithelial neoplasia tissues. Induced expression of MAFIP in HeLa cells strongly inhibited tumor formation in nude mice, confirming its tumor suppressor activity in vivo . Overexpression of MAFIP inhibited activation of the NF‐κB pathway, a commonly active pathway in cancer cells, by preventing the phosphorylation of IKK and IκBα, degradation of IκBα and the nuclear localization of p65. Induction of c‐myc , an oncogene controlled by NF‐κB, was severely impaired in the cells overexpressing MAFIP. In contrast, knockdown of MAFIP by siRNA activated the NF‐κB pathway and promoted cell proliferation. These data suggest MAFIP functions as a tumor suppressor in cervical cancer in part by inhibiting activation of the NF‐κB pathway. ( Cancer Sci 2011; 102: 2043–2050)