| First Author | Zhang W | Year | 2013 |
| Journal | Cancer Cell | Volume | 23 |
| Issue | 5 | Pages | 647-59 |
| PubMed ID | 23602409 | Mgi Jnum | J:198452 |
| Mgi Id | MGI:5496755 | Doi | 10.1016/j.ccr.2013.03.012 |
| Citation | Zhang W, et al. (2013) A NIK-IKKalpha module expands ErbB2-induced tumor-initiating cells by stimulating nuclear export of p27/Kip1. Cancer Cell 23(5):647-59 |
| abstractText | IkappaB kinase alpha (IKKalpha) activity is required for ErbB2-induced mammary tumorigenesis. Here, we show that IKKalpha and its activator, NF-kappaB-inducing kinase (NIK), support the expansion of tumor-initiating cells (TICs) that copurify with a CD24(med)CD49f(hi) population from premalignant ErbB2-expressing mammary glands. Upon activation, IKKalpha enters the nucleus, phosphorylates the cyclin-dependent kinase (CDK) inhibitor p27/Kip1, and stimulates its nuclear export or exclusion. Reduced p27 expression rescues mammary tumorigenesis in mice deficient in IKKalpha kinase activity and restores TIC self-renewal. IKKalpha is also likely to be involved in human breast cancer, where its expression shows an inverse correlation with metastasis-free survival, and its presence in the nucleus of invasive ductal carcinomas (IDCs) is associated with decreased nuclear p27 abundance. |
