Other
21 Authors
- Wu X,
- Sun Z,
- Young HA,
- Goldszmid R,
- Burkett S,
- Wiltrout RH,
- Back T,
- Jiang Q,
- Hu Y,
- Willette-Brown J,
- Schrump DS,
- Xiao Z,
- Song NY,
- Cohoon T,
- Datla M,
- Xi S,
- Zhu F,
- Pike K,
- Trinchieri G,
- Wong KK,
- Lin F
| First Author | Xiao Z | Year | 2013 |
| Journal | Cancer Cell | Volume | 23 |
| Issue | 4 | Pages | 527-40 |
| PubMed ID | 23597566 | Mgi Jnum | J:197037 |
| Mgi Id | MGI:5490686 | Doi | 10.1016/j.ccr.2013.03.009 |
| Citation | Xiao Z, et al. (2013) The pivotal role of IKKalpha in the development of spontaneous lung squamous cell carcinomas. Cancer Cell 23(4):527-40 |
| abstractText | Here, we report that kinase-dead IKKalpha knockin mice develop spontaneous lung squamous cell carcinomas (SCCs) associated with IKKalpha downregulation and marked pulmonary inflammation. IKKalpha reduction upregulated the expression of p63, Trim29, and keratin 5 (K5), which serve as diagnostic markers for human lung SCCs. IKKalpha(low)K5(+)p63(hi) cell expansion and SCC formation were accompanied by inflammation-associated deregulation of oncogenes, tumor suppressors, and stem cell regulators. Reintroducing transgenic K5.IKKalpha, depleting macrophages, and reconstituting irradiated mutant animals with wild-type bone marrow (BM) prevented SCC development, suggesting that BM-derived IKKalpha mutant macrophages promote the transition of IKKalpha(low)K5(+)p63(hi) cells to tumor cells. This mouse model resembles human lung SCCs, sheds light on the mechanisms underlying lung malignancy development, and identifies targets for therapy of lung SCCs. |
