Our group discovered a novel tumor suppressor gene now officially named MIIP (formerly known as IIp45) (Proc Natl Acad Sci USA, 100:13970-75, 2003). MIIP gene is located on 1p36.22, one of the most commonly deleted regions in a wide spectrum of cancers.
We discovered this gene during our search for a negative regulator of oncogenic protein IGFBP2. We reported in our PNAS paper that MIIP binds IGFBP2 and inhibits IGFBP2-mediated cellular migration and invasion.
With a grant from James S. McDonnell Foundation, we found and reported that MIIP counteracts HDAC6 in microtubule regulation (Journal of Biological Chemistry, 285: 3554-3560, 2010).
We showed in a collaborative study that a SNP in the MIIP gene affects risk of breast cancer (Cancer Research, 70:1024-32, 2010). We then discovered that MIIP is an important mitotic checkpoint protein and inhibits APC/Ccdc20 and block gliomagenesis (Oncogene, 29:3501-8, 2010). Our most recent studies show that the MIIP gene is frequently deleted in colorectal cancer and that MIIP mutations occur in colorectal cancer.
We also have data that show MIIP is a critical regulator for EGFR turnover in lung cancer. We have recently established a MIIP conditional knockout model and found the MIIP deletion leads to spontaneous development of lymphoma. Our continued effort in this line of research will lead to important and novel insight into this 1p36 tumor suppressor gene.
Selected Research
Song SW, Fuller GN, Khan A, Kong S, Shen W, Taylor E, Ramdas L, Lang F, and Zhang W. IIp45, an insulin-like growth factor binding protein 2 (IGFBP-2) binding protein, antagonizes IGFBP-2 stimulation of glioma cell invasion. Proc Natl Acad Sci USA 100:13970-75, 2003.
Song FF, Ji P, Zheng H, Song FJ, Wang Y, Hao X, Wei Q, Zhang W*, and Chen K*. Definition of a Functional Single Nucleotide Polymorphism in the Cell Migration Inhibitory Gene MIIP That Affects the Risk of Breast Cancer. Cancer Res. 70(3); 1024-32, 2010 *Co-corresponding author
Ji P, Smith SM, Wang YM, Jiang R, Song SW, Bruner J, Sawaya R, Kuan J, Yu HT, Fuller GN and Zhang W. Inhibition of gliomagenesis and attenuation of mitotic transition by MIIP. Oncogene 29(24):3501-8, 2010.
Wu Y, Song SW, Sun J, Bruner JM, Fuller GN, and Zhang W. IIp45 Inhibits Cell Migration through Inhibition of HDAC6. J Biol Chem 285: 3554-3560, 2010.