title: Integrin-linked kinase as a novel molecular switch of the IL-6-NF-κB signaling loop in breast cancer.
abstract: Substantial evidence has clearly demonstrated the role of the IL-6-NF-κB signaling loop in promoting aggressive phenotypes in breast cancer. However, the exact mechanism by which this inflammatory loop is regulated remains to be defined. Here, we report that integrin-linked kinase (ILK) acts as a molecular switch for this feedback loop. Specifically, we show that IL-6 induces ILK expression via E2F1 upregulation, which, in turn, activates NF-κB signaling to facilitate IL-6 production. shRNA-mediated knockdown or pharmacological inhibition of ILK disrupted this IL-6-NF-κB signaling loop, and blocked IL-6-induced cancer stem cells in vitro and estrogen-independent tumor growth in vivo Together, these findings establish ILK as an intermediary effector of the IL-6-NF-κB feedback loop and a promising therapeutic target for breast cancer.
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy , College of Pharmacy , The Ohio State University , Columbus, OH 43210 , USA.
authors.forename: En-Chi
authors.initials: EC
authors.lastname: Hsu
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy , College of Pharmacy , The Ohio State University , Columbus, OH 43210 , USA.
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Kulp
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.|Department of Pharmacology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
authors.forename: Han-Li
authors.initials: HL
authors.lastname: Huang
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.|Department of Pharmacology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
authors.forename: Huang-Ju
authors.initials: HJ
authors.lastname: Tu
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.|Department of Pharmacology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
authors.forename: Min-Wu
authors.initials: MW
authors.lastname: Chao
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy , College of Pharmacy , The Ohio State University , Columbus, OH 43210 , USA.
authors.forename: Yu-Chou
authors.initials: YC
authors.lastname: Tseng
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy , College of Pharmacy , The Ohio State University , Columbus, OH 43210 , USA.
authors.forename: Ming-Chen
authors.initials: MC
authors.lastname: Yang
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy , College of Pharmacy , The Ohio State University , Columbus, OH 43210 , USA.
authors.forename: Santosh B
authors.initials: SB
authors.lastname: Salunke
authors.affiliation: Department of Molecular Virology , Immunology , and Medical Genetics , College of Medicine , The Ohio State University , Columbus , OH 43210 , USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Sullivan
authors.affiliation: Department of Pathology , College of Medicine , National Cheng Kung University , Tainan 701 , Taiwan.
authors.forename: Wen-Chung
authors.initials: WC
authors.lastname: Chen
authors.affiliation: Center for Biostatistics , College of Medicine , The Ohio State University , Columbus , OH 43210 , USA.
authors.forename: Jianying
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology , College of Medicine , National Taiwan University , Taipei 10051 , Taiwan.
authors.forename: Che-Ming
authors.initials: CM
authors.lastname: Teng
authors.affiliation: Department of Pharmacology , College of Medicine , National Taiwan University , Taipei 10051 , Taiwan.
authors.forename: Wen-Mei
authors.initials: WM
authors.lastname: Fu
authors.affiliation: Department of Pharmaceutical Sciences , College of Pharmacy , University of Michigan , Ann Arbor , MI 48109 , USA.
authors.forename: Duxin
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Internal Medicine , University of Michigan Medical School , University of Michigan Comprehensive Cancer Center , Ann Arbor, MI 48109 , USA.
authors.forename: Max S
authors.initials: MS
authors.lastname: Wicha
authors.affiliation: Division of Hematology and Medical Oncology, Tisch Cancer Institute, Mount Sinai Medical Center , New York, NY 10029 , USA and.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Shapiro
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.|Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
authors.forename: Ching-Shih
authors.initials: CS
authors.lastname: Chen
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D015398:Signal Transduction; D000099200:Scaffold Protein ILK
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK