气候变化领域集成服务门户(CCPortal): Pharmacological inhibition of MDA-9/Syntenin blocks breast cancer metastasis through suppression of IL-1β

CCPortal

DOI	10.1073/pnas.2103180118
	Pharmacological inhibition of MDA-9/Syntenin blocks breast cancer metastasis through suppression of IL-1β
	Pradhan A.K.; Maji S.; Bhoopathi P.; Talukdar S.; Mannangatti P.; Guo C.; Wang X.-Y.; Cartagena L.C.; Idowu M.; Landry J.W.; Sarkar D.; Emdad L.; Cavenee W.K.; Das S.K.; Fisher P.B.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:21
英文摘要	Melanoma differentiation associated gene-9 (MDA-9), Syntenin-1, or syndecan binding protein is a differentially regulated prometastatic gene with elevated expression in advanced stages of melanoma. MDA-9/Syntenin expression positively associates with advanced disease stage in multiple histologically distinct cancers and negatively correlates with patient survival and response to chemotherapy. MDA-9/Syntenin is a highly conserved PDZ-domain scaffold protein, robustly expressed in a spectrum of diverse cancer cell lines and clinical samples. PDZ domains interact with a number of proteins, many of which are critical regulators of signaling cascades in cancer. Knockdown of MDA-9/Syntenin decreases cancer cell metastasis, sensitizing these cells to radiation. Genetic silencing of MDA-9/Syntenin or treatment with a pharmacological inhibitor of the PDZ1 domain, PDZ1i, also activates the immune system to kill cancer cells. Additionally, suppression of MDA-9/Syntenin deregulates myeloid-derived suppressor cell differentiation via the STAT3/interleukin (IL)1β pathway, which concomitantly promotes activation of cytotoxic T lymphocytes. Biologically, PDZ1i treatment decreases metastatic nodule formation in the lungs, resulting in significantly fewer invasive cancer cells. In summary, our observations indicate that MDA-9/ Syntenin provides a direct therapeutic target for mitigating aggressive breast cancer and a small-molecule inhibitor, PDZ1i, provides a promising reagent for inhibiting advanced breast cancer pathogenesis. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	breast cancer; IL-1β; MDA-9/Syntenin; Metastasis
语种	英语
scopus关键词	antineoplastic agent; interleukin 1beta; PDZ1 domain inhibitor; protein inhibitor; STAT3 protein; syntenin; syntenin 1; unclassified drug; antineoplastic agent; CCL11 protein, human; CCL17 protein, human; eotaxin; IL10 protein, human; IL1A protein, human; IL1B protein, human; IL23A protein, human; IL5 protein, human; interleukin 10; interleukin 1alpha; interleukin 1beta; interleukin 23p19; interleukin 5; oxadiazole derivative; pyrimidine derivative; SDCBP protein, human; syntenin; thymus and activation regulated chemokine; 4T1 cell line; animal experiment; animal model; animal tissue; Article; breast cancer; cell differentiation; cohort analysis; controlled study; cytotoxic T lymphocyte; drug targeting; ex vivo study; gene knockdown; gene silencing; lung metastasis; metastasis inhibition; mouse; myeloid-derived suppressor cell; nonhuman; tumor invasion; animal; Bagg albino mouse; breast tumor; drug effect; drug screening; female; gene expression regulation; genetics; human; immunology; lung tumor; pathology; signal transduction; synthesis; tumor cell line; tumor volume; Animals; Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Chemokine CCL11; Chemokine CCL17; Female; Gene Expression Regulation, Neoplastic; Humans; Interleukin-10; Interleukin-1alpha; Interleukin-1beta; Interleukin-23 Subunit p19; Interleukin-5; Lung Neoplasms; Mice; Mice, Inbred BALB C; Oxadiazoles; Pyrimidines; Signal Transduction; Syntenins; T-Lymphocytes, Cytotoxic; Tumor Burden; Xenograft Model Antitumor Assays
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251170
作者单位	Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, United States; Virginia Commonwealth University Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, United States; Virginia Commonwealth University Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, United States; Department of Pathology, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, United States; Ludwig Institute for Cancer Research, University of California San Diego, San diego, CA 92093, United States
推荐引用方式 GB/T 7714	Pradhan A.K.,Maji S.,Bhoopathi P.,et al. Pharmacological inhibition of MDA-9/Syntenin blocks breast cancer metastasis through suppression of IL-1β[J],2021,118(21).
APA	Pradhan A.K..,Maji S..,Bhoopathi P..,Talukdar S..,Mannangatti P..,...&Fisher P.B..(2021).Pharmacological inhibition of MDA-9/Syntenin blocks breast cancer metastasis through suppression of IL-1β.Proceedings of the National Academy of Sciences of the United States of America,118(21).
MLA	Pradhan A.K.,et al."Pharmacological inhibition of MDA-9/Syntenin blocks breast cancer metastasis through suppression of IL-1β".Proceedings of the National Academy of Sciences of the United States of America 118.21(2021).