Mechanotransduction of Primary Cilia in Lung Adenocarcinoma

Lung cancer causes more than 1 million deaths worldwide annually [1]. In a recent study by the American Cancer Society in 2011, more than 221,000 new cases of lung cancers were reported [2]. Out of these, the mortality rate was found in roughly 70% of the cases [2]. Lung cancer is divided into two major categories: small cell and non-small cell. In the United States, non-small cell lung cancer accounts for 85% of all lung cancers and is considered the most common type of lung cancer [2]. It is usually resistant to chemotherapy, therefore making it extremely difficult to treat [3]. Furthermore adenocarcinomas, a type of non-small cell lung cancer, occur towards the periphery of the lungs and are the most common type accounting for 40–45% of all lung cancer cases [3]. Epithelial cells in the healthy lungs undergo stresses during inhalation and expiration of normal breathing. In addition to the forces of normal breathing, lung cancer cells may also experience abnormal mechanical forces due to pre-existing lung diseases such as asthma, bronchitis and chronic obstructive pulmonary disease or other tumor associated structural changes. These conditions can significantly alter the structure of the lungs and cell phenotype [4]. The change in the structure of the lungs affects the mechanical environment of the cells. Changes in extracellular (ECM) stiffness, cell stretch, and shear stress influence tumorigenesis and metastasis [5]. One mechanism through which the cells sense and respond to the cellular mechanical environment is through the primary cilia [6–7]. Primary cilia are non-motile, solitary structures formed from the cellular microtubules and protrude out of each cell. They have also been shown to play an important role in facilitating common cancer signaling pathways such as Sonic Hedgehog and Wnt/β-catenin signaling [8–9]. The objective of this study was to test the hypothesis that lung cancer cells respond to mechanical stimuli with the formation of primary cilia that are necessary for 3 hallmarks of tumor progression: proliferation, epithelial mesenchymal-transition, and migration.