12:00 – 12:30 Alihamze Fathinajafabadi 

Multilevel action of AP-1 transcription factors in lung tumor microenvironment

Abstract: AP-1, a group of dimeric transcriptional complexes composed of combinations of JUN, FOS, ATF and MAF family members, plays a central role in the physiology of both individual cells and the entire organism, including embryo development and tissue homeostasis. It is involved in many cellular processes such as differentiation, proliferation, and apoptosis. Dysregulation of AP-1 protein levels and their post-translationally activated states have been implicated in various pathologies, notably tumor development. Lung cancer, particularly lung adenocarcinoma, exhibits significant involvement of AP-1 members, with the overexpression of FOSL1 and FOSL2 associated with adverse patient survival.

In our laboratory, we are investigating the multilevel actions of AP-1 activity in the lung adenocarcinoma microenvironment. Employing a combination of microscopic analysis of patient samples and in vitro approaches using related cell lines, we are assessing the protein expression patterns and intracellular localization of FRA1 (encoded by FOSL1), FRA2 (encoded by FOSL2), and JUNB. Preliminary results reveal a distinct expression pattern for these three proteins, dependent on the specific cell type within the tumor tissue. This observed differential distribution suggests a spatial-temporal coordination orchestrated by FRA1, FRA2, and JUNB between tumoral cells and specific subtypes of resident leukocytes in the tumor microenvironment, such as TANs (Tumor-Associated Neutrophils). Consequently, our findings propose a multilevel control exerted by specific AP-1 members within the tumoral context, shedding light on the intricate interplay within the lung adenocarcinoma microenvironment.