- Professor of Department of Molecular and Cellular Biology & Director of the Genetically Engineered Mouse Core, Baylor College of Medicine One Baylor Plaza, Alkek Building, Room N630.03 Mail Stop: BCM130 Houston, Texas 77030 United States
- Mol & Cell Biology-Xu
- Baylor College of Medicine
- Houston, TX, US
- Dan L Duncan Comprehensive Cancer Center
- Baylor College of Medicine
- Houston, Texas, United States
- PhD from Clarkson University/W. Alton Johns Cell Science Center
- Postdoctoral Training at Baylor College Of Medicine
- Gene networks & signaling pathways that regulate steroid hormone-promoted cancers
Overexposure and/or super sensitiveness to sex steroid hormones, such as estrogen and androgen, are risk factors that promote breast, endometrial and prostate carcinogenesis. Because of the high incidences and mortality, these steroid-promoted cancers remain to be a major threat to human health. Steroid receptors are transcription factors that depend on their coregulators to regulate specific gene expression. Each receptor can work with multiple coregulators and each coregulators also can work with multiple receptors and other types of transcription factors to regulate gene expression. In turn, these gene products are involved in various signaling pathways that control initiation, progression and metastasis of these steroid promoted cancers. Our research is mainly focused on determining the oncogenic or tumor-suppressive roles of a group of coregulators altered in breast, prostate or endometrial cancers and elucidating their molecular mechanisms for regulating the initiation, progression and metastasis of these cancers. Our ultimate goal is to identify cancer type-specific targets and pathways for the cure of steroid-promoted cancers.
Our lab is adequately equipped to execute multidisciplinary, complex studies from a single molecule to an entire mouse. In addition to common molecular, cellular and animal approaches, we routinely use many advanced technologies in our research, such as gene expression profiling, ChIP-Seq, whole genome sequencing, metabolomic profiling, Co-IP/mass spectrometry, gene knock-down/knockout/knock-in in various cell lines or mice, generation and staining of micro tissue arrays, and various kinds of xenograft/transgenic mouse models of human cancers. We have many years of experience on generating and characterization of genetically engineered mouse models.
Up to date, Dr. Xu has published ~160 peer-reviewed articles and trained 32 postdocs and 11 graduate students.
- Xu J, Liao L, Ning G, Yoshida-Komiya H, Deng C, O'Malley BW. "The steroid receptor coactivator SRC-3 (p/CIP/RAC3/AIB1/ACTR/TRAM-1) is required for normal growth, puberty, female reproductive function, and mammary gland development.." Proc. Natl. Acad. Sci. U.S.A.. 2000 June 6;97(12):6379-84. Pubmed PMID: 10823921
- Qin L, Liu Z, Chen H, Xu J. "The steroid receptor coactivator-1 regulates twist expression and promotes breast cancer metastasis.." Cancer Res.. 2009 May 1;69(9):3819-27. Pubmed PMID: 19383905
- Fu J, Qin L, He T, Qin J, Hong J, Wong J, Liao L, Xu J. "The TWIST/Mi2/NuRD protein complex and its essential role in cancer metastasis.." Cell Res.. 2011 February;21(2):275-89. Pubmed PMID: 20714342
- Qin L, Liao L, Redmond A, Young L, Yuan Y, Chen H, O'Malley BW, Xu J. "The AIB1 oncogene promotes breast cancer metastasis by activation of PEA3-mediated matrix metalloproteinase 2 (MMP2) and MMP9 expression.." Mol. Cell. Biol.. 2008 October;28(19):5937-50. Pubmed PMID: 18644862
- Qin L, Chen X, Wu Y, Feng Z, He T, Wang L, Liao L, Xu J. "Steroid receptor coactivator-1 upregulates integrin a5 expression to promote breast cancer cell adhesion and migration.." Cancer Res.. 2011 March 1;71(5):1742-51. Pubmed PMID: 21343398
- Hong J, Zhou J, Fu J, He T, Qin J, Wang L, Liao L, Xu J. "Phosphorylation of serine 68 of Twist1 by MAPKs stabilizes Twist1 protein and promotes breast cancer cell invasiveness.." Cancer Res.. 2011 June 1;71(11):3980-90. Pubmed PMID: 21502402
- Mark M, Yoshida-Komiya H, Gehin M, Liao L, Tsai MJ, O'Malley BW, Chambon P, Xu J. "Partially redundant functions of SRC-1 and TIF2 in postnatal survival and male reproduction.." Proc. Natl. Acad. Sci. U.S.A.. 2004 March 30;101(13):4453-8. Pubmed PMID: 15070739
- Xu J, Qiu Y, DeMayo FJ, Tsai SY, Tsai MJ, O'Malley BW. "Partial hormone resistance in mice with disruption of the steroid receptor coactivator-1 (SRC-1) gene.." Science. 1998 March 20;279(5358):1922-5. Pubmed PMID: 9506940
- Qin Q, Xu Y, He T, Qin C, Xu J. "Normal and disease-related biological functions of Twist1 and underlying molecular mechanisms.." Cell Res.. 2012 January;22(1):90-106. Pubmed PMID: 21876555
- Xu J, Wu RC, O'Malley BW. "Normal and cancer-related functions of the p160 steroid receptor co-activator (SRC) family.." Nat. Rev. Cancer. 2009 September;9(9):615-30. Pubmed PMID: 19701241
- Kuang SQ, Liao L, Wang S, Medina D, O'Malley BW, Xu J. "Mice lacking the amplified in breast cancer 1/steroid receptor coactivator-3 are resistant to chemical carcinogen-induced mammary tumorigenesis.." Cancer Res.. 2005 September 1;65(17):7993-8002. Pubmed PMID: 16140972
- Liu Z, Zhou S, Liao L, Chen X, Meistrich M, Xu J. "Jmjd1a demethylase-regulated histone modification is essential for cAMP-response element modulator-regulated gene expression and spermatogenesis.." J. Biol. Chem.. 2010 January 22;285(4):2758-70. Pubmed PMID: 19910458
- Zhang H, Kuang SQ, Liao L, Zhou S, Xu J. "Haploid inactivation of the amplified-in-breast cancer 3 coactivator reduces the inhibitory effect of peroxisome proliferator-activated receptor gamma and retinoid X receptor on cell proliferation and accelerates polyoma middle-T antigen-induced mammary t." Cancer Res.. 2004 October 1;64(19):7169-77. Pubmed PMID: 15466215
- Yuan Y, Qin L, Liu D, Wu RC, Mussi P, Zhou S, Songyang Z, Xu J. "Genetic screening reveals an essential role of p27kip1 in restriction of breast cancer progression.." Cancer Res.. 2007 September 1;67(17):8032-42. Pubmed PMID: 17804714
- Chung AC, Zhou S, Liao L, Tien JC, Greenberg NM, Xu J. "Genetic ablation of the amplified-in-breast cancer 1 inhibits spontaneous prostate cancer progression in mice.." Cancer Res.. 2007 June 15;67(12):5965-75. Pubmed PMID: 17575167
- Wang S, Yuan Y, Liao L, Kuang SQ, Tien JC, O'Malley BW, Xu J. "Disruption of the SRC-1 gene in mice suppresses breast cancer metastasis without affecting primary tumor formation.." Proc. Natl. Acad. Sci. U.S.A.. 2009 January 6;106(1):151-6. Pubmed PMID: 19109434
- Kuang SQ, Liao L, Zhang H, Pereira FA, Yuan Y, DeMayo FJ, Ko L, Xu J. "Deletion of the cancer-amplified coactivator AIB3 results in defective placentation and embryonic lethality.." J. Biol. Chem.. 2002 November 22;277(47):45356-60. Pubmed PMID: 12368298
- Kuang SQ, Liao L, Zhang H, Lee AV, O'Malley BW, Xu J. "AIB1/SRC-3 deficiency affects insulin-like growth factor I signaling pathway and suppresses v-Ha-ras-induced breast cancer initiation and progression in mice.." Cancer Res.. 2004 March 1;64(5):1875-85. Pubmed PMID: 14996752
- Chen X, Liu Z, Xu J. "The cooperative function of nuclear receptor coactivator 1 (NCOA1) and NCOA3 in placental development and embryo survival.." Mol. Endocrinol.. 2010 October;24(10):1917-34. Pubmed PMID: 20685850
- Yuan Y, Liao L, Tulis DA, Xu J. "Steroid receptor coactivator-3 is required for inhibition of neointima formation by estrogen.." Circulation. 2002 June 4;105(22):2653-9. Pubmed PMID: 12045172
- Li Q, Chu MJ, Xu J. "Tissue- and nuclear receptor-specific function of the C-terminal LXXLL motif of coactivator NCoA6/AIB3 in mice.." Mol. Cell. Biol.. 2007 December;27(23):8073-86. Pubmed PMID: 17908797
- Xu J, Nawaz Z, Tsai SY, Tsai MJ, O'Malley BW. "The extreme C terminus of progesterone receptor contains a transcriptional repressor domain that functions through a putative corepressor.." Proc. Natl. Acad. Sci. U.S.A.. 1996 October 29;93(22):12195-9. Pubmed PMID: 8901556
- Louet JF, Chopra AR, Sagen JV, An J, York B, Tannour-Louet M, Saha PK, Stevens RD, Wenner BR, Ilkayeva OR, Bain JR, Zhou S, DeMayo F, Xu J, Newgard CB, O'Malley BW. "The coactivator SRC-1 is an essential coordinator of hepatic glucose production.." Cell Metab.. 2010 December 1;12(6):606-18. Pubmed PMID: 21109193
- Liao L, Dearth RK, Zhou S, Britton OL, Lee AV, Xu J. "Liver-specific overexpression of the insulin-like growth factor-I enhances somatic growth and partially prevents the effects of growth hormone deficiency.." Endocrinology. 2006 August;147(8):3877-88. Pubmed PMID: 16709615
- Weiss RE#, Xu J#, Ning G, Pohlenz J, O’Malley BW, and Refetoff S. "Mice deficient in the steroid receptor coactivator-1 (SRC-1) are resistant to thyroid hormone." EMBO J. 1999;18:1900-4.
- Puigserver P, Adelmant G, Wu Z, Fan M, Xu J, O'Malley B, Spiegelman BM. "Activation of PPARgamma coactivator-1 through transcription factor docking.." Science. 1999 November 12;286(5443):1368-71. Pubmed PMID: 10558993
- Nishihara E, Yoshida-Komiya H, Chan CS, Liao L, Davis RL, O'Malley BW, Xu J. "SRC-1 null mice exhibit moderate motor dysfunction and delayed development of cerebellar Purkinje cells.." J. Neurosci.. 2003 January 1;23(1):213-22. Pubmed PMID: 12514218
- Zhang H, Liao L, Kuang SQ, Xu J. "Spatial distribution of the messenger ribonucleic acid and protein of the nuclear receptor coactivator, amplified in breast cancer-3, in mice.." Endocrinology. 2003 April;144(4):1435-43. Pubmed PMID: 12639927
- Xu J, Li Q. "Review of the in vivo functions of the p160 steroid receptor coactivator family.." Mol. Endocrinol.. 2003 September;17(9):1681-92. Pubmed PMID: 12805412
- Mussi P, Yu C, O'Malley BW, Xu J. "Stimulation of steroid receptor coactivator-3 (SRC-3) gene overexpression by a positive regulatory loop of E2F1 and SRC-3.." Mol. Endocrinol.. 2006 December;20(12):3105-19. Pubmed PMID: 16916939
- Mussi P, Liao L, Park SE, Ciana P, Maggi A, Katzenellenbogen BS, Xu J, O'Malley BW. "Haploinsufficiency of the corepressor of estrogen receptor activity (REA) enhances estrogen receptor function in the mammary gland.." Proc. Natl. Acad. Sci. U.S.A.. 2006 November 7;103(45):16716-21. Pubmed PMID: 17065319
- Yu C, York B, Wang S, Feng Q, Xu J, O'Malley BW. "An essential function of the SRC-3 coactivator in suppression of cytokine mRNA translation and inflammatory response.." Mol. Cell. 2007 March 9;25(5):765-78. Pubmed PMID: 17349961
- Yuan Y, Xu J. "Loss-of-function deletion of the steroid receptor coactivator-1 gene in mice reduces estrogen effect on the vascular injury response.." Arterioscler. Thromb. Vasc. Biol.. 2007 July;27(7):1521-7. Pubmed PMID: 17446438
- Liao L, Chen X, Wang S, Parlow AF, Xu J. "Steroid receptor coactivator 3 maintains circulating insulin-like growth factor I (IGF-I) by controlling IGF-binding protein 3 expression.." Mol. Cell. Biol.. 2008 April;28(7):2460-9. Pubmed PMID: 18212051
- Liu Z, Liao L, Zhou S, Xu J. "Generation and validation of a mouse line with a floxed SRC-3/AIB1 allele for conditional knockout.." Int. J. Biol. Sci.. 2008;4(4):202-7. Pubmed PMID: 18690289
- Chopra AR, Louet JF, Saha P, An J, Demayo F, Xu J, York B, Karpen S, Finegold M, Moore D, Chan L, Newgard CB, O'Malley BW. "Absence of the SRC-2 coactivator results in a glycogenopathy resembling Von Gierke's disease.." Science. 2008 November 28;322(5906):1395-9. Pubmed PMID: 19039140
- York B, Yu C, Sagen JV, Liu Z, Nikolai BC, Wu RC, Finegold M, Xu J, O'Malley BW. "Reprogramming the posttranslational code of SRC-3 confers a switch in mammalian systems biology.." Proc. Natl. Acad. Sci. U.S.A.. 2010 June 15;107(24):11122-7. Pubmed PMID: 20534466
- York B, Reineke EL, Sagen JV, Nikolai BC, Zhou S, Louet JF, Chopra AR, Chen X, Reed G, Noebels J, Adesina AM, Yu H, Wong LJ, Tsimelzon A, Hilsenbeck S, Stevens RD, Wenner BR, IIkayeva O, Xu J, Newgard CB, O’Malley BW. "Ablation of steroid receptor coactivator-3 resembles the human CACT metabolic myopathy." Cell Metab. 2012;15(5):752-63.
- Zhou J, Qin L, Gao L, Chen X, Tien JCY, Wang F, Hsieh J-T, Xu J. "Nkx3.1 functions as a “Para-Transcription Factor” to regulate gene expression and cell proliferation in a non-cell-autonomous manner." J Biol Chem. 2012;287:17248-56.
- Chen LY, Zhang Y, Zhang Q, Li H, Luo Z, Fang H, Kim SH, Qin L, Yotnda P, Xu J, Tu BP, Bai Y, Songyang Z. "Mitochondrial localization of telomeric protein TIN2 links telomere regulation to metabolic control." Mol Cell. 2012;47(6):839-50.
- Kawagoe J, Li Q, Mussi P, Liao L, Lydon JP, DeMayo FJ and Xu J. "Nuclear receptor coactivator-6 attenuates uterine estrogen sensitivity to permit embryo implantation." Dev Cell. 2012;23:858-65.
- Tien JC, Liu Z, Liao L, Wang F, Xu Y, Wu YL, Zhou N, Ittmann M, Xu J. "The steroid receptor coactivator-3 is required for the development of castration-resistant prostate cancer." Cancer Res. 2013;73(13):3997-4008.
- Xu Y, Xu Y, Liao L, Zhou Z, Theissen S, Liao X-H, Nguyen H, Ludwig T, Qin L, Martinez J, Jiang J, Xu J. "Inducible knockout of Twist1 in young and adult mice prolongs hair growth cycle and has mild effects on general health, supporting Twist1 as a preferential cancer target." Am J Pathol. 2013;183(4):1281-92.
- Wang Y, Lonard DM, Yu Y, Chow DC, Palzkill TG, Wang J, Qi R, Matzuk AJ, Song X, Madoux F, Hodder P, Chase P, Griffin PR, Zhou S, Liao L, Xu J, O'Malley BW. "Bufalin Is a Potent Small-Molecule Inhibitor of the Steroid Receptor Coactivators SRC-3 and SRC-1." Cancer Res. 2014;74(5):1506-17.
- Qin L, Wu YL, Toneff MJ, Li D, Liao L, Gao X, Bane FT, Tien J, Xu Y, Feng Z, Yang Z, Xu Y, Theissen SM, Li Y, Young L, Xu J. "NCOA1 directly targets M-CSF1 expression to promote breast cancer metastasis." Cancer Res. 2014;74:3477-88.
- Lee DK, Liu Y, Liao L, Wang F, Xu J. "The prostate basal cell (BC) heterogeneity and the p63-positive BC differentiation spectrum in mice." Int J Biol Sci. 2014;10(9):1007-17.
- Tien J, Liao L, Liu Y, Liu Z, Lee DK, Wang F, Xu J. "The steroid receptor coactivator-3 is required for developing neuroendocrine tumor in mice." Int J Biol Sci. 2014;10(10):1116-27.
- Ma G, He J, Yu Y, Xu Y, Yu X, Martinez J, Lonard DM, Xu J. "Tamoxifen Inhibits ER-negative Breast Cancer Cell Invasion and Metastasis by Accelerating Twist1 Degradation." Int J Biol Sci. 2015;11(5):618-28.
- Wang L, Yu Y, Chow DC, Yan F, Hsu CC, Stossi F, Mancini MA, Palzkill T, Liao L, Zhou S, Xu J, Lonard DM, O’Malley BW. "Overactivation of the p160 SRCs by the small molecular inhibitor MCB-613 causes cancer cell stress and paraptosis." Cancer Cell. 2015;28(2):240-52.
- Gao L, Rabbitt EH, Condon JC, Renthal NE, Mitsche MA, Chambon P, Xu J, O’Malley BW, Mendelson CR. "Steroid receptor coactivators 1 and 2 mediate fetal-to-maternal signaling that initiates parturition." J Clin Invest. 2015;125(7):2808-24.
- Qin L, Xu Y, Xu Y, Ma G, Liao L, Wu Y, Li Y, Wang X, Wang X, Jiang J, Wang J, Xu J. "NCOA1 Promotes Angiogenesis in Breast Tumors by Simultaneously Enhancing both HIF1α- and AP-1-mediated VEGFa Transcription." Oncotarget. 2015;6(27):11518-28.
- Sun T, Fu J, Shen T, Lin X, Liao L, Feng XH, Xu J. "The small C-terminal domain phosphatase 1 inhibits cancer cell migration and invasion by dephosphorylating phospho-Ser68-Twist1 to accelerate Twist1 degradation." J Biol Chem. 2015;291(22):11518-28.
- Song X, Chen J, Zhao M, Zhang C, Yu Y, Lonard DM, Chow DC, Palzkill T, Xu J, O’Malley BW, Wang J. "Development of potent small-molecular inhibitors to drug the undruggable steroid receptor coactivator-3." Proc Natl Acad Sci USA. 2016;113(18):4970-5.
- Welte T, Kim IS, Tian L, Gao X, Wang H, Li J, Holdman XB, Herschkowitz JI, Pond A, Xie G, Kurley S, Nguyen T, Liao L, Dobrolecki LE, Pang L, Mo Q, Edwards DP, Huang S, Xin L, Xu J, Li Y, Lewis MT, Wang T, Westbrook TF, Rosen JM, Zhang XH. "Oncogenic mTOR signaling recruits myeloid-derived suppressor cells to promote tumour initiation." Nat Cell Biol. 2016;18(6):632-44.
- Xu Y, Qin L, Sun T, Wu H, He T, Yang Z, Mo Q, Liao L, Xu J. "Twist1 Promotes Breast Cancer Invasion and Metastasis by Silencing Foxa1 Expression. Oncogene." Oncogene. 2016;ePub ahead of print