Mouse lung cancer single cell RNA-seq

Single cell RNA-seq of mouse lung tumors.Integrins, the principal extracellular matrix (ECM) receptors of the cell, promote cell adhesion, migration, and proliferation, which are key events for cancer growth and metastasis. To date, most integrin-targeted therapeutics have disrupted integrin-ECM interactions, which are viewed as critical for integrin functions. However, such agents have failed to improve cancer patient outcomes. We show that integrin beta1, a highly expressed subunit in lung epithelium, is required for lung adenocarcinoma development in a carcinogen-induced mouse model. Likewise, human lung adenocarcinoma cell lines with integrin beta1 deletion failed to form colonies in soft agar and tumors in mice. Mechanistically, we demonstrate that these effects do not require integrin beta1-mediated adhesion to ECM but are dependent on integrin beta1 cytoplasmic tail-mediated activation of focal adhesion kinase (FAK). Together, these studies support a critical role for integrin beta1 in lung tumorigenesis that is mediated through constitutive, ECM-binding independent signaling involving the cytoplasmic tail.