Surprisingly, loss of <i>Smad4</i>, a key mediator of Tgfbr2, failed to drive lung SCC; instead, low levels of phosphorylated ERK1/2, a Smad-independent downstream effector of Tgfbr2, were tightly associated with lung SCC in both mouse and human.
We previously showed that targeting Kras(G12D) activation and transforming growth factor β receptor type II (TGFβRII) deletion to airway basal cells via a keratin promoter induced formation of both lung AdC and SCC.
TGFβRII deletion in mouse airway epithelial cells promotes adenocarcinoma and SCC formation, indicating that TGFβRII loss plays a causal role in lung carcinogenesis.