Presentation description

Lung adenocarcinoma (LUAD) is the most prevalent subtype of non-small cell lung cancer (NSCLC), accounting for about 40% of all lung cancers. Within the Tumor Microenvironment (TME) in cancerous Lung Tissue, tumor growth alters the mechanical input that can potentially affect surrounding cells, including the Fibroblasts in the native lung tissue. Fibroblasts are known for their vital roles in maintaining the integrity of the Extracellular matrix (ECM) by secreting ECM proteins, aiding tissue remodeling, and wound healing. Excessive ECM production, like TNC, COL1, etc., is prognostic for poor survival in LUAD patients. Numerous studies have also shown that upregulated α-SMA expression is a viable marker for activated fibroblasts. We focused on testing how strain regulates the biochemical pathway of Rho-Actin/ MRTF to generate ECM, with TNC serving as readout. The impact is that determining and targeting the cellular components that participate in the strain-regulated ECM production will contribute towards combating LUAD progression and improving overall patients' survival. The question we have when approaching this project is: How does cyclic mechanical strain in the lung tumor microenvironment (TME) influence fibroblast activation and the expression of extracellular matrix proteins during LUAD progression? We hypothesize, based on the background of this project, that that tumor growth in the TCM increases mechanical strain in Lung Adenocarcinoma, and this may activate lung fibroblasts to express higher levels of α-SMA and other ECM proteins due to strain-induced remodeling of the cytoskeletal pathways. We performed several experiments to determine different aspects of the pathway, including the knockdown of MRTFA through western blotting and through our pharmacological inhibition of Rho activity using the small-molecule inhibitor (Y27632) against ROCK, a downstream molecule of Rho GTPase. This would allow us to determine and compare the effect two different blocking mechanisms has on the same pathway and which one is more effective. Stretching does play a role.