Unknown

Dataset Information

0

The pivotal role of IKK? in the development of spontaneous lung squamous cell carcinomas.

ABSTRACT: Here, we report that kinase-dead IKK? knockin mice develop spontaneous lung squamous cell carcinomas (SCCs) associated with IKK? downregulation and marked pulmonary inflammation. IKK? reduction upregulated the expression of p63, Trim29, and keratin 5 (K5), which serve as diagnostic markers for human lung SCCs. IKK?(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.IKK?, depleting macrophages, and reconstituting irradiated mutant animals with wild-type bone marrow (BM) prevented SCC development, suggesting that BM-derived IKK? mutant macrophages promote the transition of IKK?(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.

SUBMITTER: Xiao Z 

PROVIDER: S-EPMC3649010 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Here, we report that kinase-dead IKKα knockin mice develop spontaneous lung squamous cell carcinomas (SCCs) associated with IKKα downregulation and marked pulmonary inflammation. IKKα reduction upregulated the expression of p63, Trim29, and keratin 5 (K5), which serve as diagnostic markers for human lung SCCs. IKKα(low)K5(+)p63(hi) cell expansion and SCC formation were accompanied by inflammation-associated deregulation of oncogenes, tumor suppressors, and stem cell regulators. Reintroducing tra  ...[more]

Similar Datasets

Proteomics Lung squamous cell carcinomas & papillary predominant adenocarcinomas
2021-07-19 | PXD027381 | JPOST Repository
Unknown Molecular homology between canine spontaneous oral squamous cell carcinomas and human head-and-neck squamous cell carcinomas reveals disease drivers and therapeutic vulnerabilities.
| S-EPMC7642746 | biostudies-literature
Unknown EZH2 Inhibition Promotes Tumor Immunogenicity in Lung Squamous Cell Carcinomas.
| S-EPMC10863487 | biostudies-literature
Unknown EZH2 inhibition promotes tumor immunogenicity in lung squamous cell carcinomas.
| S-EPMC10274685 | biostudies-literature
Unknown Role of deltaNp63(pos)CD44v(pos) cells in the development of N-nitroso-tris-chloroethylurea-induced peripheral-type mouse lung squamous cell carcinomas.
| S-EPMC4768398 | biostudies-literature
Unknown Arsenic-related DNA copy-number alterations in lung squamous cell carcinomas.
| S-EPMC2967055 | biostudies-literature
Unknown Understanding the molecular association between hyperkalemia and lung squamous cell carcinomas.
| S-EPMC7579872 | biostudies-literature
Unknown Genetic alteration profiling of patients with resected squamous cell lung carcinomas.
| S-EPMC5095023 | biostudies-literature
Unknown A critical role for I kappaB kinase alpha in the development of human and mouse squamous cell carcinomas.
| S-EPMC1859910 | biostudies-literature
Proteomics Targeted Proteomics of Lung Squamous Cell Carcinomas
2023-07-09 | PXD040680 | panorama