TSPAN2 Is Involved in Cell Invasion and Motility during Lung Cancer Progression

In lung cancer progression, p53 mutations are more often observed in invasive tumors than in noninvasive tumors, suggesting that p53 is involved in tumor invasion and metastasis. To understand the nature of p53 function as a tumor suppressor, it is crucial to elucidate the detailed mechanism of the alteration in epithelial cells that follow oncogenic KRAS activation and p53 inactivation. Here, we report that KRAS activation induces epithelial-mesenchymal transition and that p53 inactivation is required for cell motility and invasiveness. Furthermore, TSPAN2, a transmembrane protein, is responsible for cell motility and invasiveness elicited by p53 inactivation. TSPAN2 is highly expressed in p53-mutated lung cancer cells, and high expression of TSPAN2 is associated with the poor prognosis of lung adenocarinomas. TSPAN2 knockdown suppresses metastasis to the lungs and liver, enabling prolonged survival. TSPAN2 enhances cell motility and invasiveness by assisting CD44 in scavenging intracellular reactive oxygen species. [Display omitted] •KRAS activation is linked to EMT in small airway epithelial cells•p53 inactivation, but not KRAS activation, enhances cell invasion and motility•TSPAN2 is identified as a factor responsible for invasion, motility, and metastasis•TSPAN2 assists a ROS-scavenging function of CD44 to promote cell invasion Enari and colleagues investigate the detailed mechanism of epithelial cell alteration during lung cancer progression. They show that KRAS activation induces epithelial-mesenchymal transition and that p53 inactivation is required for cell motility and invasiveness. They find that TSPAN2 is responsible for the cell motility and invasiveness elicited by p53 inactivation and that TSPAN2 scavenges intracellular reactive oxygen species in collaboration with CD44. These data suggest that TSPAN2 may be a potential target for lung cancer therapy.