| First Author | Yin N | Year | 2019 |
| Journal | Cancer Cell | Volume | 36 |
| Issue | 2 | Pages | 156-167.e7 |
| PubMed ID | 31378680 | Mgi Jnum | J:278962 |
| Mgi Id | MGI:6359681 | Doi | 10.1016/j.ccell.2019.07.002 |
| Citation | Yin N, et al. (2019) Protein Kinase Ciota and Wnt/beta-Catenin Signaling: Alternative Pathways to Kras/Trp53-Driven Lung Adenocarcinoma. Cancer Cell 36(2):156-167.e7 |
| abstractText | We report that mouse LSL-Kras(G12D);Trp53(fl/fl) (KP)-mediated lung adenocarcinoma (LADC) tumorigenesis can proceed through both PKCiota-dependent and PKCiota-independent pathways. The predominant pathway involves PKCiota-dependent transformation of bronchoalveolar stem cells (BASCs). However, KP mice harboring conditional knock out Prkci alleles (KPI mice) develop LADC tumors through PKCiota-independent transformation of Axin2(+) alveolar type 2 (AT2) stem cells. Transformed growth of KPI, but not KP, tumors is blocked by Wnt pathway inhibition in vitro and in vivo. Furthermore, a KPI-derived genomic signature predicts sensitivity of human LADC cells to Wnt inhibition, and identifies a distinct subset of primary LADC tumors exhibiting a KPI-like genotype. Thus, LADC can develop through both PKCiota-dependent and PKCiota-independent pathways, resulting in tumors exhibiting distinct oncogenic signaling and pharmacologic vulnerabilities. |
