State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
Cancer Sci. 2011 Nov;102(11):2043-50. doi: 10.1111/j.1349-7006.2011.02061.x. Epub 2011 Sep 15.
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.
宫颈癌是女性中第二常见的癌症。肿瘤抑制基因的失活是宫颈癌转化和进展的基础。此前，我们报道了 MAFIP 可以抑制人宫颈癌 HeLa 细胞的生长。本研究发现 MAFIP 在宫颈上皮内瘤变组织中下调。在 HeLa 细胞中诱导表达 MAFIP 强烈抑制裸鼠肿瘤形成，证实了其在体内的肿瘤抑制活性。MAFIP 的过表达通过阻止 IKK 和 IκBα 的磷酸化、IκBα 的降解和 p65 的核定位来抑制 NF-κB 通路的激活，NF-κB 通路是癌细胞中常见的活性通路。受 NF-κB 控制的癌基因 c-myc 的诱导严重受损在过表达 MAFIP 的细胞中。相反，用 siRNA 敲低 MAFIP 激活了 NF-κB 通路并促进了细胞增殖。这些数据表明 MAFIP 作为宫颈癌的肿瘤抑制因子，部分通过抑制 NF-κB 通路的激活发挥作用。
