Gumireddy Kiranmai, Li Anping, Kossenkov Andrew V, Cai Kathy Q, Liu Qin, Yan Jinchun, Xu Hua, Showe Louise, Zhang Lin, Huang Qihong
The Wistar Institute, Philadelphia, Pennsylvania.
Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
Mol Cancer Res. 2014 Sep;12(9):1334-43. doi: 10.1158/1541-7786.MCR-14-0049. Epub 2014 Jun 19.
Metastasis is a major factor responsible for mortality in patients with breast cancer. Inhibitor of DNA binding 1 (Id1) has been shown to play an important role in cell differentiation, tumor angiogenesis, cell invasion, and metastasis. Despite the data establishing Id1 as a critical factor for lung metastasis in breast cancer, the pathways and molecular mechanisms of Id1 functions in metastasis remain to be defined. Here, we show that Id1 interacts with TFAP2A to suppress S100A9 expression. We show that expression of Id1 and S100A9 is inversely correlated in both breast cancer cell lines and clinical samples. We also show that the migratory and invasive phenotypes in vitro and metastasis in vivo induced by Id1 expression are rescued by reestablishment of S100A9 expression. S100A9 also suppresses the expression of known metastasis-promoting factor RhoC activated by Id1 expression. Our results suggest that Id1 promotes breast cancer metastasis by the suppression of S100A9 expression.
Novel pathways by Id1 regulation in metastasis.
转移是导致乳腺癌患者死亡的主要因素。DNA结合抑制因子1（Id1）已被证明在细胞分化、肿瘤血管生成、细胞侵袭和转移中起重要作用。尽管有数据表明Id1是乳腺癌肺转移的关键因素，但Id1在转移中发挥作用的途径和分子机制仍有待确定。在此，我们表明Id1与TFAP2A相互作用以抑制S100A9的表达。我们发现Id1和S100A9的表达在乳腺癌细胞系和临床样本中呈负相关。我们还表明，通过重建S100A9的表达可挽救由Id1表达诱导的体外迁移和侵袭表型以及体内转移。S100A9还抑制由Id1表达激活的已知转移促进因子RhoC的表达。我们的结果表明，Id1通过抑制S100A9的表达促进乳腺癌转移。
Id1调控转移的新途径。
