Jianming Xu, Ph.D.
Department of Molecular and Cellular Biology
Ph.D.: Clarkson University, Potsdam
Postdoctoral training: Baylor College of Medicine, Houston
Transcriptional Control of Development and Hormonally Promoted Breast and Prostate Cancers
Our research is to define the role and molecular mechanisms of a group of specific transcription factors and their coregulators in transcriptional control of development, organ function and hormonally promoted breast and prostate cancers. In our study, we use multidisciplinary state-of-art technologies, such as genetically manipulated mouse models, retrovirus-mediated genome wide mutagenesis, proteomics, metabolomics, 3-D culture, and molecular, cellular and histological methodologies. We have three research directions.
- To investigate the in vivo functions of nuclear receptor coactivators through generation and characterization of knockout and transgenic mice. Our study is focused on several coactivators including three members in the steroid receptor coactivator (SRC) family, the cancer-amplified coactivator AIB3 and the histone H3 K9 demethylases. Conventional, conditional and combinatorial gene-targeted mouse lines for SRC-1, SRC-2, SRC-3/AIB1 and AIB3 have been generated to study their roles in development and organ functions. These animal models also provide information regarding the pathological roles of these gene mutations in human diseases.
- To define the roles for nuclear receptor coactivators in hormonally promoted breast and prostate cancers. By inducing breast and prostate tumorigenesis with oncogenes and carcinogens in our knockout and transgenic mice, we have discovered that SRC-1 promotes breast cancer progression, but not initiation; SRC-3 promotes breast cancer initiation and progression; and SRC-3 also strongly promotes prostate cancer progression. Our ongoing work is to investigate the molecular mechanisms responsible for these coregulators in control of breast and prostate cancer initiation, progression and metastasis, using animal and cell culture models as well as biochemical approaches.
- To uncover molecular mechanisms governing cancer progression and metastasis. One of the sub-aims is to identify genes and associated mechanisms responsible for breast cancer progression from estrogen dependence to estrogen independence and tamoxifen resistance. Through inducing genome-wide mutagenesis by specially designed retroviruses, we intend to identify genes whose loss- or gain-of-function mutations result in tamoxifen resistance. We have reported that disruption of p27 creates antiestrogen resistance and promotes breast cancer progression. The other sub-aim is to investigate transcriptional control of breast cancer metastasis by Twist. Twist is one of the master regulators for cancer metastasis and an E-box-binding transcription factor that can both repress and activate gene expression. Our study is to understand the molecular mechanisms responsible for Twist to control metastasis.
Baylor College of Medicine
One Baylor Plaza, Alkek N630.03
Houston, TX 77030
- Zhou J, Qin L, Gao L, Chen X, Tien JCY, Wang F, Hsieh J-T, Xu J. (2012) Nkx3.1 Functions as Para-Transcription Factor to Regulate Gene Expression and Cell Proliferation in Non-cell-autonomous Manner. J Biol Chem 287:17248-56.
- Qin L, Chen X, Wu Y, Feng Z, He T, Wang L, Liao L, Xu J. (2011) Steroid receptor coactivator-1 upregulates integrin 5 expression to promote breast cancer cell adhesion and migration. Cancer Res 71(5):1742-51.
- Fu J, Qin L, He T, Qin J, Hong J, Wong J, Liao L and Xu J. (2011) The TWIST/Mi2/NuRD Protein Complex and its Essential Role in Cancer Metastasis. Cell Res 21:275-289.
- Hong J, Zhou J, Fu J, He T, Qin J, Wang L, Liao L and Xu J. (2011) MAP kinase-mediated Twist1 phosphorylation at serine 68 stabilizes Twist1 protein and promotes breast cancer invasiveness. Cancer Res 71(11):3980-90.
- Xu J, Wu RC, O’Malley BW. (2009) Normal and cancer-related functions of the p160 steroid receptor coactivator family. Nat Rev Cancer 9:615-630.
- Qin L, Zhaoliang LZ, Chen H, and Xu J. (2009). The Steroid Receptor Coactivator-1 (SRC-1) Regulates Twist Expression and Promotes Breast Cancer Metastasis. Cancer Res. 69:3819-27.
- Wang S, Yuan Y, Liao L, Kuang S-Q, Tien JCY, O’Malley BW, and Xu J. (2009). Disruption of the Steroid Receptor Coactivator-1 (SRC-1) Gene in Mice Suppresses Breast Cancer Metastasis without Affecting Primary Tumor Formation. Proc. Natl. Acad. Sci. USA 106:151-6.
- Qin L, Liao L, Redmond A, Young L, Yuan Y, Chen H, O’Malley BW, and Xu J. (2008). The AIB1 oncogene promotes breast cancer metastasis by activation of PEA3-mediated MMP2 and MMP9 expression. Mol. Cell. Biol. 28: 5937-50.
- Yuan Y, Qin L, Liu D, Wu RC, Mussi P, Zhou S, Songyang Z, and Xu J. (2007). Genetic screening reveals an essential role of p27kip1 in restriction of breast cancer progression. Cancer Res. 67:8032-42.
- Chung ACK, Zhou S, Liao L, Tien JCY, Greenberg NM, and Xu J. (2007). Genetic ablation of the amplified-in-breast cancer-1 inhibits spontaneous prostate cancer progression in mice. Cancer Res. 67:5965-75.