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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.

Lin Zhang, Ph.D.

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

��Reversible�� tumor suppressor loss: key to new brain cancer therapies?

Dr. Lin Zhang and colleagues found that PTEN is regulated by different organs, which is a problem for patients with brain metastases as PTEN in cells is shut off in the brain. However, PTEN is restored once cells migrate to other organs. This discovery could be promising for developing effective new anti-metastasis therapies for late-stage brain cancer patients.

Other Articles

Yuzhalin AE, Lowery F, Saito Y, Yuan X, Yao J, Duan Y, Ding J, Acharya S, Fajardo A, Chen HN, Wei Y,Sun Y, Zhang L, Xiao Y, Li P, Lorenzi PL, Huse JT, Fan H, Zhao Z, Hung MC, Yu D. Astrocyte-induced Cdk5 expedites breast cancer brain metastasis by suppressing MHC-I expression to evade immune recognition. Nat Cell Biol. In Press.

. 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.
. EZH2 engages TGF�� signaling to promote breast cancer bone metastasis via integrin ��1-FAK activation. Nat Commun 13(1):2543, 2022. e-Pub 2022. PMID: 35538070.
. 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.
. 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.
. Blocking immunosuppressive neutrophils deters pY696-EZH2-driven brain metastases. Sci Transl Med 12(545), 2020. PMID: 32461334.
. 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.
. Sphingosine Kinase 1 Signaling Promotes Metastasis of Triple-Negative Breast Cancer. Cancer Res 79(16):4211-4226, 2019. e-Pub 2019. PMID: 31239273.
. 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.
. 14-3-3�� 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.
. 14-3-3�� Loss Impedes Oncogene-induced Mammary Tumorigenesis and Metastasis by Attenuating Oncogenic Signaling. Am J Cancer Res 7(8):1654�C1664, 2017. e-Pub 2017. PMID: 28861322.
. Upregulation of Lactate Dehydrogenase A by 14-3-3�� Leads to Increased Glycolysis Critical for Breast Cancer Initiation and Progression. Oncotarget 7(23):35270-35283. e-Pub 2016. PMID: 27150057.
. Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth. Nature 527(7576):100-4, 2015. e-Pub 2015. PMID: 26479035.
. 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.
. 14-3-3�� Turns TGF-��'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.
. 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.
. 14-3-3�� Orchestrates Mammary Tumor Onset and Progression via miR-221-Mediated Cell Proliferation. Cancer Res 74(1):363-73, 2014. e-Pub 2013. PMID: 24197133.
. Enhanced PI3K p110�� Signaling Confers Acquired Lapatinib Resistance That Can Be Effectively Reversed by a p110��-Selective PI3K Inhibitor. Mol Cancer Ther 13(1):60-70, 2014. PMID: 24249715.
. 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.
. 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.
. The Skp2-SCF E3 Ligase Regulates Akt Ubiquitination, Glycolysis, Herceptin Sensitivity, and Tumorigenesis. Cell 149(5):1098-111, 2012. PMID: 22632973.
. 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.
. 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.
. 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.
. 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.
. 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.
. 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.
. 14-3-3�� 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.
. 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.
. 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.
. 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.
. Upregulation of CXCR4 is essential for HER2-mediated tumor metastasis. . Cancer Cell 6(5):459-469, 2004. PMID: 15542430.
. 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.
. 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.
. Overexpression of ErbB2 blocks Taxol-induced apoptosis by upregulation of p21Cip1, which inhibits p34Cdc2 kinase. Mol Cell 2(5):581-91, 1998. PMID: 9844631.
. 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.
. 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.
. 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.
. Adenovirus type 5 E1A gene products act as transformation suppressors of the neu oncogene. Mol Cell Biol 11(3):1745-50, 1991. PMID: 1671710.
. 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.

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Publications

Antihistamines can influence immunotherapy response by enhancing T cell activation Nov. 24, 2021

Brain metastases recruit suppressive immune cells via novel pathway to facilitate their growth

��Reversible�� tumor suppressor loss: key to new brain cancer therapies?

��Jekyll and Hyde�� protein both prevents and spreads cancer Feb. 9, 2015

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Antihistamines can influence immunotherapy response by enhancing T cell activation
Nov. 24, 2021

��Jekyll and Hyde�� protein both prevents and spreads cancer
Feb. 9, 2015