Abstract：
:We report that mouse LSL-KrasG12D;Trp53fl/fl (KP)-mediated lung adenocarcinoma (LADC) tumorigenesis can proceed through both PKCι-dependent and PKCι-independent pathways. The predominant pathway involves PKCι-dependent transformation of bronchoalveolar stem cells (BASCs). However, KP mice harboring conditional knock out Prkci alleles (KPI mice) develop LADC tumors through PKCι-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 PKCι-dependent and PKCι-independent pathways, resulting in tumors exhibiting distinct oncogenic signaling and pharmacologic vulnerabilities.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Yin N,Liu Y,Khoor A,Wang X,Thompson EA,Leitges M,Justilien V,Weems C,Murray NR,Fields APdoi
10.1016/j.ccell.2019.07.002subject
Has Abstractpub_date
2019-08-12 00:00:00pages
156-167.e7issue
2eissn
1535-6108issn
1878-3686pii
S1535-6108(19)30329-0journal_volume
36pub_type
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