Abstract
BackgroundBoth 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.ResultsIn 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.ConclusionsOur 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.
Highlights
Both IB kinase (IKK) complex and oncgenic protein Myc play important roles in cancer progression, including cancer cell invasiveness and metastasis
The expression of Myc is associated with IKKs but not with NF-B in breast cancer To identify whether the expression of Myc was associated with IKKs/NF-B expressions in vivo, Immunohistochemical study (IHC) staining was used to identify the expression of IKKa, IKKb, Myc and NF-B p65 in a total of 21 breast cancer specimens
Statistical analysis showed that Myc expression was correlated with IKKa and IKKb expression, whereas it had no correlation with the expression of NF-B p65 (Figure 1)
Summary
Both IB kinase (IKK) complex and oncgenic protein Myc play important roles in cancer progression, including cancer cell invasiveness and metastasis. The IKK complex is composed of two kinase catalytic subunits IKKa and IKKb and a non-kinase scaffold protein IKKg [1,2,3]. The complex functions as an upstream kinase involved in the activation of nuclear factor kappa B(NF-B)by phosphorylation of the NF-B inhibitory molecule, IBa, resulting in the subsequent degradation of IBa through the ubiqutin/proteasome pathway. Numerous reports have indicated that the functions of IKKs are necessary for cancer cell survival and progression [3,6,7,8]. Accumulating evidence has indicated that IKKs have NF-Bindependent effects on multiple proteins [1,10].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
