Abstract 5231: GAS6 signaling links smoke-filled environments to increased invasion and communication in gastric and lung cancer models

Abstract A key determinant of cancer severity is its invasion potential—the ability of malignant cells to spread from their primary site across a border and establish secondary tumors in distant tissues. One major environmental factor commonly seen in society today is the use of stimulants, such as nicotine and other nicotine-containing substances. Nicotine has been found to influence the pathogenesis of many different cancer types including lung cancer, gastric cancer, and many other types. In addition to the neurological effects, scientists have identified a gene that encodes for a gamma-carboxyglutamic acid-containing protein (known as GAS6) that has been found to play a role in cell proliferation. Additionally, GAS6 is found to have a role in the inflammation and immune effects that contribute to the invasion potential of cancer. To determine that GAS6 affects the cell invasion potential and increase cell proliferation, we altered the environment of gastric adenocarcinoma cells (AGS) and human alveolar basal epithelial adenocarcinoma cells (A549) by infusing smoke from both cigarettes and electronic cigarettes, found to increase GAS6 levels , as well as GAS6 specifically into the cell culture media. We then isolated exosomes, nano-sized extracellular vesicles containing proteins, lipids, and more derived from their parent cells. Exosomes have emerged as critical mediators in cancer progression due to their essential roles in tumor growth, immune modulation, and the metastatic process, making them a significant focus of current cancer research. In doing so, we found that GAS6 increased cell proliferation, exosome production, and invasion potential in gastric and cancer cell lines, suggesting the potential of GAS6 as a biomarker for invasive potential in cancer cell types. Citation Format: Emilee N. Humphreys, Derek Clarke, Kristen Noyes, Madeline Boyer, Juan Arroyo, Amber Gonda. GAS6 signaling links smoke-filled environments to increased invasion and communication in gastric and lung cancer models abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5231.