IκB kinases increase Myc protein stability and enhance progression of breast cancer cells
Journal
Molecular Cancer
Journal Volume
10
Date Issued
2011
Author(s)
Abstract
Background: Both IκB kinase (IKK) complex and oncgenic protein Myc play important roles in cancer progression, including cancer cell invasiveness and metastasis. The levels of Myc is regulated by the phosphorylation of Myc at Thr58 and Ser62.Results: In this study, we show that the expression of Myc is associated with IKKα and IKKβ in breast cancers and that Myc is an IKKs substrate. Suppression of IKK activity by either chemical inhibitor or transfection of kinase-dead mutants decreases the phosphorylation of Myc at Ser62 and enhances the degradation of Myc. Consequently, these treatments decrease the tumorigenic and invasive ability of breast cancer cells. Furthermore, doxorubicin, a frequently used anticancer drug in breast cancer, activates IKKs and Myc, thereby increasing invasiveness and tumorigenesis of breast carcinoma MCF7 cells. Inhibition of IKKs prevents these doxorubicin-induced effects.Conclusions: Our study indicates that IKKs tightly regulate Myc expression through prolonging protein stability, and suggests that IKKs are potentially therapeutic targets and that suppression of IKKs may be used following chemotherapy to reduce the risk of treatment-induced tumor progression. ? 2011 Yeh et al; licensee BioMed Central Ltd.
SDGs
Other Subjects
antineoplastic agent; bay 110782; cyclin D1; doxorubicin; I kappa B alpha; I kappa B beta; immunoglobulin enhancer binding protein; messenger RNA; Myc protein; transcription factor Twist; unclassified drug; 3 (4 methylphenylsulfonyl) 2 propenenitrile; 3-(4-methylphenylsulfonyl)-2-propenenitrile; antineoplastic agent; doxorubicin; I kappa B kinase; immunoglobulin enhancer binding protein; Myc protein; nitrile; sulfone; article; breast cancer; cancer growth; cancer invasion; carcinogenesis; cell proliferation; cell strain MCF 7; genetic transfection; human; human tissue; immunohistochemistry; protein degradation; protein expression; protein localization; protein phosphorylation; protein protein interaction; protein stability; signal transduction; breast tumor; cell motion; cell transformation; disease course; drug antagonism; drug effect; enzymology; female; genetics; metabolism; physiology; protein binding; protein stability; RNA stability; tumor cell line; Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Cell Transformation, Neoplastic; Disease Progression; Doxorubicin; Female; Humans; I-kappa B Kinase; NF-kappa B; Nitriles; Protein Binding; Protein Stability; Proto-Oncogene Proteins c-myc; RNA Stability; RNA, Messenger; Signal Transduction; Sulfones
Type
journal article