Publications
"Histamine, through its receptor HRH1, can promote cancer cell immune evasion and resistance to immunotherapy."
~Yi Xiao, Ph.D.
We present an effective strategy to target immunosuppressive neutrophils to treat brain metastases using available therapies that could be fast-tracked into clinical studies.
This research found that metastatic cancer cells in the brain upregulate expression of the EZH2 gene to activate a previously unknown pathway and recruit immune-suppressive neutrophils to the brain, allowing metastatic cells to thrive. This suggests that targeting this neutrophil recruitment may be a useful strategy for treating brain metastases
Other Articles
- Yuan X, Duan Y, Xiao Y, Sun K, Qi Y, Zhang Y, Ahmed Z, Moiani D, Yao J, Li H, Zhang L, Yuzhalin AE, Li P, Zhang C, Badu-Nkansah A, Saito Y, Liu X, Kuo WL, Ying H, Sun SC, Chang JC, Tainer JA, Yu D. Vitamin E Enhances Cancer Immunotherapy by Reinvigorating Dendritic Cells via Targeting Checkpoint SHP1. Cancer Discov 12(7):1742-1759, 2022. e-Pub 2022. PMID: 35420681.
- Zhang L, Qu J, Qi Y, Duan Y, Huang YW, Zhou Z, Li P, Yao J, Huang B, Zhang S, Yu D. EZH2 engages TGFβ signaling to promote breast cancer bone metastasis via integrin β1-FAK activation. Nat Commun 13(1):2543, 2022. e-Pub 2022. PMID: 35538070.
- Li H, Xiao Y, Li Q, Yao J, Yuan X, Zhang Y, Yin X, Saito Y, Fan H, Li P, Kuo WL, Halpin A, Gibbons DL, Yagita H, Zhao Z, Pang D, Ren G, Yee C, Lee JJ, Yu D. The allergy mediator histamine confers resistance to immunotherapy in cancer patients via activation of the macrophage histamine receptor H1. Cancer Cell 40(1):36-52.e9, 2022. e-Pub 2021. PMID: 34822775.
- Wang J, Zhang Y, Xiao Y, Yuan X, Li P, Wang X, Duan Y, Seewaldt VL, Yu D. Boosting immune surveillance by low-dose PI3K inhibitor facilitates early intervention of breast cancer. Am J Cancer Res 11(5):2005-2024, 2021. e-Pub 2021. PMID: 34094666.
- Zhang L, Yao J, Wei Y, Zhou Z, Li P, Qu J, Badu-Nkansah A, Yuan X, Huang YW, Fukumura K, Mao X, Chang WC, Saunus J, Lakhani S, Huse JT, Hung MC, Yu D. Blocking immunosuppressive neutrophils deters pY696-EZH2-driven brain metastases. Sci Transl Med 12(545), 2020. PMID: 32461334.
- Yuzhalin AE, Lim SY, Gordon-Weeks AN, Fischer R, Kessler BM, Yu D, Muschel RJ. Proteomics analysis of the matrisome from MC38 experimental mouse liver metastases. Am J Physiol Gastrointest Liver Physiol 317(5):G625-G639, 2019. e-Pub 2019. PMID: 31545917.
- Acharya S, Yao J, Li P, Zhang C, Lowery FJ, Zhang Q, Guo H, Qu J, Yang F, Wistuba II, Piwnica-Worms H, Sahin AA, Yu D. Sphingosine Kinase 1 Signaling Promotes Metastasis of Triple-Negative Breast Cancer. Cancer Res 79(16):4211-4226, 2019. e-Pub 2019. PMID: 31239273.
- Zhou Z, Li M, Zhang L, Zhao H, Sahin Ö, Chen J, Zhao JJ, Songyang Z, Yu D. Oncogenic kinase-induced PKM2 tyrosine 105 phosphorylation converts non-oncogenic PKM2 to a tumor promoter and induces cancer stem-like cells. Cancer Res 78(9):2248-2261, 2018. e-Pub 2018. PMID: 29440169.
- Yang J, Joshi S, Wang Q, Li P, Wang H, Xiong Y, Xiao Y, Wang J, Parker-Thornburg J, Behringer RR, Yu D. 14-3-3ζ Loss Leads to Neonatal Lethality by MicroRNA-126 Downregulation-Mediated Developmental Defects in Lung Vasculature. Cell Biosci 7:58, 2017. e-Pub 2017. PMID: 29118970.
- Joshi S, Yang J, Wang Q, Li P, Wang H, Zhang Q, Xiong Y, Pickering BF, Parker-Thornburg J, Behringer RR, Yu D. 14-3-3ζ Loss Impedes Oncogene-induced Mammary Tumorigenesis and Metastasis by Attenuating Oncogenic Signaling. Am J Cancer Res 7(8):1654–1664, 2017. e-Pub 2017. PMID: 28861322.
- Chang CC, Zhang C, Zhang Q, Sahin O, Wang H, Xu J, Xiao Y, Zhang J, Rehman SK, Li P, Hung MC, Behbod F, Yu D. Upregulation of Lactate Dehydrogenase A by 14-3-3ζ Leads to Increased Glycolysis Critical for Breast Cancer Initiation and Progression. Oncotarget 7(23):35270-35283. e-Pub 2016. PMID: 27150057.
- Zhang L, Zhang S, Yao J, Lowery FJ, Zhang Q, Huang WC, Li P, Li M, Wang X, Zhang C, Wang H, Ellis K, Cheerathodi M, McCarty JH, Palmieri D, Saunus J, Lakhani S, Huang S, Sahin AA, Aldape KD, Steeg PS, Yu D. Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth. Nature 527(7576):100-4, 2015. e-Pub 2015. PMID: 26479035.
- Jain S, Wang X, Chang CC, Ibarra-Drendall C, Wang H, Zhang Q, Brady SW, Li P, Zhao H, Dobbs J, Kyrish M, Tkaczyk TS, Ambrose A, Sistrunk C, Arun BK, Richards-Kortum R, Jia W, Seewaldt VL, Yu D. Src Inhibition Blocks c-Myc Translation and Glucose Metabolism to Prevent the Development of Breast Cancer. Cancer Res 75(22):4863-75, 2015. e-Pub 2015. PMID: 26383165.
- Brady SW, Zhang J, Li P, Tsai MH, Yu D. PI3K-independent mTOR activation promotes lapatinib resistance and IAP expression that can be effectively reversed by mTOR and Hsp90 inhibition. Cancer Biology and Therapy 16(3):402-411, 2015.
- Xu J, Acharya S, Sahin O, Zhang Q, Saito Y, Yao J, Wang H, Li P, Zhang L, Lowery FJ, Kuo WL, Xiao Y, Ensor J, Sahin AA, Zhang XH, Hung MC, Zhang JD, Yu D. 14-3-3ζ Turns TGF-β's Function from Tumor Suppressor to Metastasis Promoter in Breast Cancer by Contextual Changes of Smad Partners from p53 to Gli2. Cancer Cell 27(2):177-92, 2015. PMID: 25670079.
- Sahin O, Wang Q, Brady SW, Ellis K, Wang H, Chang CC, Zhang Q, Priya P, Zhu R, Wong ST, Landis MD, Muller WJ, Esteva FJ, Chang J, Yu D. Biomarker-guided sequential targeted therapies to overcome therapy resistance in rapidly evolving highly aggressive mammary tumors. Cell Res 24(5):542-59, 2014. e-Pub 2014. PMID: 24675532.
- Rehman SK, Li SH, Wyszomierski SL, Wang Q, Li P, Sahin O, Xiao Y, Zhang S, Xiong Y, Yang J, Wang H, Guo H, Zhang JD, Medina D, Muller WJ, Yu D. 14-3-3ζ Orchestrates Mammary Tumor Onset and Progression via miR-221-Mediated Cell Proliferation. Cancer Res 74(1):363-73, 2014. e-Pub 2013. PMID: 24197133.
- Brady SW, Zhang J, Seok D, Wang H, Yu D. Enhanced PI3K p110α Signaling Confers Acquired Lapatinib Resistance That Can Be Effectively Reversed by a p110α-Selective PI3K Inhibitor. Mol Cancer Ther 13(1):60-70, 2014. PMID: 24249715.
- Zhang S, Huang WC, Zhang L, Zhang C, Lowery FJ, Ding Z, Guo H, Wang H, Huang S, Sahin AA, Aldape KD, Steeg PS, Yu D. Src family kinases as novel therapeutic targets to treat breast cancer brain metastases. Cancer Res 73(18):5764-74, 2013. e-Pub 2013. PMID: 23913825.
- Wang Q, Li SH, Wang H, Xiao Y, Sahin O, Brady SW, Li P, Ge H, Jaffee EM, Muller WJ, Hortobagyi GN, Yu D. Concomitant targeting of tumor cells and induction of T cell response synergizes to effectively inhibit trastuzumab-resistant breast cancer. Cancer Res 72(17):4417-4428, 2012. e-Pub 2012. PMID: 22773664.
- Chan CH, Li CF, Yang WL, Gao Y, Lee SW, Feng Z, Huang HY, Tsai KK, Flores LG, Shao Y, Hazle JD, Yu D, Wei W, Sarbassov D, Hung MC, Nakayama KI, Lin HK. The Skp2-SCF E3 Ligase Regulates Akt Ubiquitination, Glycolysis, Herceptin Sensitivity, and Tumorigenesis. Cell 149(5):1098-111, 2012. PMID: 22632973.
- Pickering BF, *Yu D, Van Dyke MW. Nucleolin protein interacts with microprocessor complex to affect biogenesis of microRNAs 15a and 16. J Biol Chem 286(51):44095-103, 2011. e-Pub 2011. PMID: 22049078.
- Morrow PK, Wulf GM, Ensor J, Booser DJ, Moore JA, Flores PR, Xiong Y, Zhang S, Krop IE, Winer EP, Kindelberger DW, Coviello J, Sahin AA, Nuñez R, Hortobagyi GN, Yu D, Esteva FJ. Phase I/II Study of Trastuzumab in Combination With Everolimus (RAD001) in Patients With HER2-Overexpressing Metastatic Breast Cancer Who Progressed on Trastuzumab-Based Therapy. J Clin Oncol 29(23):3126-32, 2011. e-Pub 2011. PMID: 21730275.
- Zhang S, Huang WC, Li P, Guo H, Poh SB, Brady SW, Xiong Y, Tseng LM, Li SH, Ding Z, Sahin AA, Esteva FJ, Hortobagyi GN, Yu D. Combating trastuzumab resistance by targeting SRC, a common node downstream of multiple resistance pathways. Nat Med 17(4):461-9, 2011. e-Pub 2011. PMID: 21399647.
- Chang CJ, Chao CH, Xia W, Yang JY, Xiong Y, Li CW, Yu WH, Rehman SK, Hsu JL, Lee HH, Liu M, Chen CT, Yu D, Hung MC. p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs. Nat Cell Biol 13(3):317-23, 2011. e-Pub 2011. PMID: 21336307.
- Esteva FJ, Guo H, Zhang S, Santa-Maria C, Stone S, Lanchbury JS, Sahin AA, Hortobagyi GN, Yu D. PTEN, PIK3CA, p-AKT, and p-p70S6K status: association with trastuzumab response and survival in patients with HER2-positive metastatic breast cancer. Am J Pathol 177(4):1647-56, 2010. e-Pub 2010. PMID: 20813970.
- Lu J, Guo H, Treekitkarnmongkol W, Li P, Zhang J, Shi B, Ling C, Zhou X, Chen T, Chiao PJ, Feng X, Seewaldt VL, Muller WJ, Sahin A, Hung MC, Yu D. 14-3-3zeta Cooperates with ErbB2 to Promote Ductal Carcinoma In Situ Progression to Invasive Breast Cancer by Inducing Epithelial-Mesenchymal Transition. Cancer Cell 16(3):195-207, NIHMS[140388], 2009. PMID: 19732720.
- Neal CL, Yao J, Yang W, Zhou X, Nguyen NT, Lu J, Danes CG, Guo H, Lan KH, Ensor J, Hittelman W, Hung MC, Yu D. 14-3-3ζ Overexpression Defines High Risk for Breast Cancer Recurrence and Promotes Cancer Cell Survival. Cancer Res 69(8):3425-32, 2009. e-Pub 2009. PMID: 19318578.
- Lu CH, Wyszomierski SL, Tseng LM, Sun MH, Lan KH, Neal CL, Mills GB, Hortobagyi GN, Esteva FJ, Yu D. Preclinical testing of clinically applicable strategies for overcoming trastuzumab resistance caused by PTEN deficiency. Clin Can Res 13:5883-8, 2007. *Accompanied by Preview: Ellis M, PIKing the winner for PI3 kinase inhibitors in ErbB2 positive breast cancer: let's Not PTENed it's easy! Clin Can Res 13:5661-2. Clin Cancer Res 13(19):5883-8, 2007. PMID: 17908983.
- Tan M, Lan KH, Yao J, Lu CH, Sun M, Neal CL, Lu J, Yu D. Selective inhibition of ErbB2-overexpressing breast cancer in vivo by a novel TAT-based ErbB2-targeting signal transducers and activators of transcription 3-blocking peptide. Cancer Res 66(7):3764-72, 2006. PMID: 16585203.
- Klos KS, Wyszomierski SL, Sun M, Tan M, Zhou X, Li P, Yang W, Yin G, Hittelman WN, Yu D. ErbB2 increases vascular endothelial growth factor protein synthesis via activation of mammalian target of rapamycin/p70S6K leading to increased angiogenesis and spontaneous metastasis of human breast cancer cells. Cancer Res 66(4):2028-37, 2006. PMID: 16489002.
- Li Y, Pan Y, Wei Y, Cheng X, Zhou B, Tan M, Zhou X, Xia W, Hortobagyi GN, Yu D, Hung M-C. Upregulation of CXCR4 is essential for HER2-mediated tumor metastasis. . Cancer Cell 6(5):459-469, 2004. PMID: 15542430.
- Nagata Y, Lan KH, Zhou X, Tan M, Esteva FJ, Sahin AA, Klos KS, Li P, Monia BP, Nguyen NT, Hortobagyi GN, Hung MC, Yu D. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell 6:117-27, 2004. *Accompanied by Preview: Crowder RJ, Lombardi DP, Ellis MJ. Successful targeting of ErbB2 receptors - is PTEN the key? Cell 6: 103-4, 2004. * Accompanied by Nature news: Pearson H, Nature, Aug 23, 2004. *Accompanied by News and Commentary: Pandolfi PP. N Engl J Med 351:2337. Cancer Cell 6(2):117-27, 2004. PMID: 15324695.
- Tan M, Jing T, Lan KH, Neal CL, Li P, Lee S, Fang D, Nagata Y, Liu J, Arlinghaus R, Hung MC, Yu D. Phosphorylation on tyrosine-15 of p34(Cdc2) by ErbB2 inhibits p34(Cdc2) activation and is involved in resistance to taxol-induced apoptosis. Mol Cell 9(5):993-1004, 2002. PMID: 12049736.
- Yu D, Jing T, Liu B, Yao J, Tan M, McDonnell TJ, Hung MC. Overexpression of ErbB2 blocks Taxol-induced apoptosis by upregulation of p21Cip1, which inhibits p34Cdc2 kinase. Mol Cell 2(5):581-91, 1998. PMID: 9844631.
- Liu B, Sun D, Xia W, Hung MC, Yu D. Cross-reactivity of C219 anti-p170(mdr-1) antibody with p185(c-erbB2) in breast cancer cells: cautions on evaluating p170(mdr-1), J. Natl. Cancer Inst. 89: 1524-9,1997. Accompanied by Editorial: Chan HS, Ling V, Anti-P-glycoprotein Antibody C219 Cross-reactivity with c-erbB2 Protein: Diagnostic and Clinical Implications. J Natl Cancer Inst 89(20):1473-1475, 1997. PMID: 9337349.
- Tan M, Yao J, Yu D. Overexpression of the c-erbB-2 gene enhanced intrinsic metastasis potential in human breast cancer cells without increasing their transformation abilities. Cancer Res 57(6):1199-205, 1997. PMID: 9067293.
- Yu D, Wang SS, Dulski KM, Tsai CM, Nicolson GL, Hung MC. c-erbB-2/neu overexpression enhances metastatic potential of human lung cancer cells by induction of metastasis-associated properties. Cancer Res 54(12):3260-6, 1994. PMID: 7911396.
- Yu D, Scorsone K, Hung MC. Adenovirus type 5 E1A gene products act as transformation suppressors of the neu oncogene. Mol Cell Biol 11(3):1745-50, 1991. PMID: 1671710.
- Yu D, Suen TC, Yan DH, Chang LS, Hung MC. Transcriptional repression of the neu protooncogene by the adenovirus 5 E1A gene products. Proc Natl Acad Sci U S A 87(12):4499-503, 1990. PMID: 1972274.